Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2017, Article ID 1720920, 13 pages
https://doi.org/10.1155/2017/1720920
Review Article

The Role of Adenosine A2A Receptor, CYP450s, and PPARs in the Regulation of Vascular Tone

1Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506, USA
2Department of Pharmaceutical Chemistry, School of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia

Correspondence should be addressed to Mohammed A. Nayeem; ude.uvw.csh@meeyanm

Received 19 April 2017; Revised 22 June 2017; Accepted 12 July 2017; Published 13 August 2017

Academic Editor: Hugo Gutiérrez-De-Terán

Copyright © 2017 Maan T. Khayat and Mohammed A. Nayeem. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. Sandoo, J. J. C. S. V. van Zanten, G. S. Metsios, D. Carroll, and G. D. Kitas, “The endothelium and its role in regulating vascular tone,” The Open Cardiovascular Medicine Journal, vol. 4, pp. 302–312, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. B. M. Egan, Y. Zhao, and R. N. Axon, “US trends in prevalence, awareness, treatment, and control of hypertension, 1988–2008,” The Journal of the American Medical Association, vol. 303, no. 20, pp. 2043–2050, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. L.-W. Lehman, M. Saeed, G. Moody, and R. Mark, “Hypotension as a risk factor for acute kidney injury in ICU patients,” Computing in Cardiology, vol. 37, pp. 1095–1098, 2010. View at Google Scholar · View at Scopus
  4. C. A. Hübner, B. C. Schroeder, and H. Ehmke, “Regulation of vascular tone and arterial blood pressure: role of chloride transport in vascular smooth muscle,” Pflugers Archiv European Journal of Physiology, vol. 467, no. 3, pp. 605–614, 2015. View at Publisher · View at Google Scholar · View at Scopus
  5. C. M. Lawes, S. V. Hoorn, and A. Rodgers, “Global burden of blood-pressure-related disease, 2001,” The Lancet, vol. 371, no. 9623, pp. 1513–1518, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. D. Konukoglu and H. Uzun, Endothelial Dysfunction and Hypertension, Springer, Boston, Mass, USA.
  7. M. S. Fernández-Alfonso, “Regulation of vascular tone: The fat connection,” Hypertension, vol. 44, no. 3, pp. 255-256, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. D. B. Cines, E. S. Pollak, C. A. Buck et al., “Endothelial cells in physiology and in the pathophysiology of vascular disorders,” Blood, vol. 91, no. 10, pp. 3527–3561, 1998. View at Google Scholar · View at Scopus
  9. L. Ghitescu and M. Robert, “Diversity in unity: The biochemical composition of the endothelial cell surface varies between the vascular beds,” Microscopy Research and Technique, vol. 57, no. 5, pp. 381–389, 2002. View at Publisher · View at Google Scholar · View at Scopus
  10. H. G. Augustin, D. H. Kozian, and R. C. Johnson, “Differentiation of endothelial cells: Analysis of the constitutive and activated endothelial cell phenotypes,” BioEssays, vol. 16, no. 12, pp. 901–906, 1994. View at Publisher · View at Google Scholar · View at Scopus
  11. H. Wolinsky, “A proposal linking clearance of circulating lipoproteins to tissue metabolic activity as a basis for understanding atherogenesis,” Circulation Research, vol. 47, no. 3, pp. 301–311, 1980. View at Publisher · View at Google Scholar · View at Scopus
  12. R. Jay Widmer and A. Lerman, “Endothelial dysfunction and cardiovascular disease,” Global Cardiology Science and Practice, vol. 2014, no. 3, pp. 291–308, 2014. View at Publisher · View at Google Scholar
  13. R. P. Brandes, F.-H. Schmitz-Winnenthal, M. Félétou et al., “An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 17, pp. 9747–9752, 2000. View at Publisher · View at Google Scholar · View at Scopus
  14. M. A. Nayeem, D. S. Ponnoth, M. A. Boegehold, D. C. Zeldin, J. R. Falck, and S. J. Mustafa, “High-salt diet enhances mouse aortic relaxation through adenosine A2A receptor via CYP epoxygenases,” American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol. 296, no. 3, pp. R567–R574, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. M. A. Nayeem, S. M. Poloyac, J. R. Falck et al., “Role of CYP epoxygenases in A2A AR-mediated relaxation using A2A AR-null and wild-type mice,” American Journal of Physiology - Heart and Circulatory Physiology, vol. 295, no. 5, pp. H2068–H2078, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. M. A. Nayeem, D. C. Zeldin, M. A. Boegehold et al., “Modulation by salt intake of the vascular response mediated through adenosine A2A receptor: role of CYP epoxygenase and soluble epoxide hydrolase,” American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol. 299, no. 1, pp. R325–R333, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. W. T. Wong, S. L. Wong, X. Y. Tian, and Y. Huang, “Endothelial dysfunction: The common consequence in diabetes and hypertension,” Journal of Cardiovascular Pharmacology, vol. 55, no. 4, pp. 300–307, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. M. Félétou and P. M. Vanhoutte, “Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture),” American Journal of Physiology: Heart and Circulatory Physiology, vol. 291, no. 3, pp. H985–H1002, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. D. H. Endemann and E. L. Schiffrin, “Endothelial dysfunction,” Journal of the American Society of Nephrology, vol. 15, no. 8, pp. 1983–1992, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Taddei, L. Ghiadoni, A. Virdis, D. Versari, and A. Salvetti, “Mechanisms of endothelial dysfunction: Clinical significance and preventive non-pharmacological therapeutic strategies,” Current Pharmaceutical Design, vol. 9, no. 29, pp. 2385–2402, 2003. View at Publisher · View at Google Scholar · View at Scopus
  21. M. H. Laughlin, S. C. Newcomer, and S. B. Bender, “Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype,” Journal of Applied Physiology, vol. 104, no. 3, pp. 588–600, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. W. T. Cade, “Diabetes-related microvascular and macrovascular diseases in the physical therapy setting,” Physical Therapy, vol. 88, no. 11, pp. 1322–1335, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. F. Addabbo, M. Montagnani, and M. S. Goligorsky, “Mitochondria and reactive oxygen species,” Hypertension, vol. 53, no. 6, pp. 885–892, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. A. Hirose, T. Tanikawa, H. Mori, Y. Okada, and Y. Tanaka, “Advanced glycation end products increase endothelial permeability through the RAGE/Rho signaling pathway,” FEBS Letters, vol. 584, no. 1, pp. 61–66, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. P. Rajendran, T. Rengarajan, J. Thangavel et al., “The vascular endothelium and human diseases,” International Journal of Biological Sciences, vol. 9, no. 10, pp. 1057–1069, 2013. View at Publisher · View at Google Scholar
  26. M. A. Gimbrone, “Vascular endothelium, hemodynamic forces, and atherogenesis,” American Journal of Pathology, vol. 155, no. 1, pp. 1–5, 1999. View at Publisher · View at Google Scholar · View at Scopus
  27. M. A. Gimbrone, “The Gordon wilson lecture: understanding vascular endothelium: a pilgrim's progress: endothelial dysfunction, biomechanical forces and the pathobiology of atherosclerosis,” Transactions of the American Clinical and Climatological Association, vol. 121, pp. 115–127, 2010. View at Google Scholar · View at Scopus
  28. P. Libby, P. M. Ridker, and G. K. Hansson, “Inflammation in atherosclerosis: from pathophysiology to practice,” Journal of the American College of Cardiology, vol. 54, no. 23, pp. 2129–2138, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. C. S. T. Hilaire, S. H. Carroll, H. Chen, and K. Ravid, “Mechanisms of induction of adenosine receptor genes and its functional significance,” Journal of Cellular Physiology, vol. 218, no. 1, pp. 35–44, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. G. Shaikh and B. Cronstein, “Signaling pathways involving adenosine A(2A) and A(2B) receptors in wound healing and fibrosis,” Purinergic Signalling, vol. 12, no. 2, pp. 191–197, 2016. View at Publisher · View at Google Scholar · View at Scopus
  31. M. A. Nayeem, M. A. Boegehold, and S. J. Mustafa, “Adenosine A2A receptor mediated aortic relaxation in mice fed high salt: role of CYP epoxygenase,” The FASEB Journal, vol. 21, no. 6, pp. A899–A900, 2007. View at Google Scholar
  32. M. A. Nayeem, I. Pradhan, S. J. Mustafa, C. Morisseau, J. R. Falck, and D. C. Zeldin, “Adenosine A2A receptor modulates vascular response in soluble epoxide hydrolase-null mice through CYP-epoxygenases and PPARγ,” American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol. 304, no. 1, pp. R23–R32, 2013. View at Publisher · View at Google Scholar · View at Scopus
  33. M. A. Nayeem, D. C. Zeldin, M. A. Boegehold, and J. R. Falck, “Salt modulates vascular response through adenosine A(2A) receptor in eNOS-null mice: Role of CYP450 epoxygenase and soluble epoxide hydrolase,” Molecular and Cellular Biochemistry, vol. 350, no. 1-2, pp. 101–111, 2011. View at Publisher · View at Google Scholar · View at Scopus
  34. M. A. Nayeem, G. P. Matherne, and S. J. Mustafa, “Ischemic and pharmacological preconditioning induces further delayed protection in transgenic mouse cardiac myocytes over-expressing adenosine A1 receptors (A1AR): Role of A1AR, iNOS and K(ATP) channels,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 367, no. 3, pp. 219–226, 2003. View at Publisher · View at Google Scholar · View at Scopus
  35. H. Labazi, S. L. Tilley, C. Ledent, and S. J. Mustafa, “Role of adenosine receptor(s) in the control of vascular tone in the mouse pudendal artery,” Journal of Pharmacology and Experimental Therapeutics, vol. 356, no. 3, pp. 673–680, 2016. View at Publisher · View at Google Scholar · View at Scopus
  36. K. Fuxe, D. O. Borroto-Escuela, W. Romero-Fernandez et al., “On the role of volume transmission and receptor-receptor interactions in social behaviour: Focus on central catecholamine and oxytocin neurons,” Brain Research, vol. 1476, pp. 119–131, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. G. Navarro, D. O. Borroto-Escuela, K. Fuxe, and R. Franco, “Purinergic signaling in Parkinson's disease. Relevance for treatment,” Neuropharmacology, vol. 104, pp. 161–168, 2016. View at Publisher · View at Google Scholar · View at Scopus
  38. D. O. Borroto-Escuela, J. Carlsson, P. Ambrogini et al., “Understanding the role of gpcr heteroreceptor complexes in modulating the brain networks in health and disease,” Frontiers in Cellular Neuroscience, vol. 11, p. 37, 2017. View at Publisher · View at Google Scholar
  39. L. T. Woods, D. Ajit, J. M. Camden, L. Erb, and G. A. Weisman, “Purinergic receptors as potential therapeutic targets in Alzheimer's disease,” Neuropharmacology, vol. 104, pp. 169–179, 2016. View at Publisher · View at Google Scholar
  40. M. Matos, H.-Y. Shen, E. Augusto et al., “Deletion of adenosine A2A receptors from astrocytes disrupts glutamate homeostasis leading to psychomotor and cognitive impairment: relevance to Schizophrenia,” Biological Psychiatry, vol. 78, no. 11, pp. 763–774, 2015. View at Publisher · View at Google Scholar · View at Scopus
  41. X. Guitart, J. Bonaventura, W. Rea et al., “Equilibrative nucleoside transporter ENT1 as a biomarker of Huntington disease,” Neurobiology of Disease, vol. 96, pp. 47–53, 2016. View at Publisher · View at Google Scholar · View at Scopus
  42. A. Rahman, “The role of adenosine in Alzheimer's disease,” Current Neuropharmacology, vol. 7, no. 3, pp. 207–216, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. B. B. Fredholm, A. P. IJzerman, K. A. Jacobson, K. N. Klotz, and J. Linden, “International union of pharmacology. XXV. Nomenclature and classification of adenosine receptors,” Pharmacological Reviews, vol. 53, no. 4, pp. 527–552, 2001. View at Google Scholar
  44. J. Linden, “Structure and function of A1 adenosine receptors,” FASEB Journal, vol. 5, no. 12, pp. 2668–2676, 1991. View at Google Scholar · View at Scopus
  45. A. M. Sebastião and J. A. Ribeiro, “Adenosine A2 receptor-mediated excitatory actions on the nervous system,” Progress in Neurobiology, vol. 48, no. 3, pp. 167–189, 1996. View at Publisher · View at Google Scholar · View at Scopus
  46. D. Boison, “Adenosine as a neuromodulator in neurological diseases,” Current Opinion in Pharmacology, vol. 8, no. 1, pp. 2–7, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. X. X. Li, T. Nomura, H. Aihara, and T. Nishizaki, “Adenosine enhances glial glutamate efflux via A2a adenosine receptors,” Life Sciences, vol. 68, no. 12, pp. 1343–1350, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Melani, S. Cipriani, M. G. Vannucchi et al., “Selective adenosine A2A receptor antagonism reduces JNK activation in oligodendrocytes after cerebral ischaemia,” Brain, vol. 132, no. 6, pp. 1480–1495, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. B. D. Hettinger, A. Lee, J. Linden, and D. L. Rosin, “Ultrastructural localization of adenosine A2A receptors suggests multiple cellular sites for modulation of GABAergic neurons in rat striatum,” Journal of Comparative Neurology, vol. 431, no. 3, pp. 331–346, 2001. View at Publisher · View at Google Scholar · View at Scopus
  50. B. B. Fredholm, A. P. IJzerman, K. A. Jacobson, J. Linden, and C. E. Müller, “International union of basic and clinical pharmacology. LXXXI. Nomenclature and classification of adenosine receptors—an update,” Pharmacological Reviews, vol. 63, no. 1, pp. 1–34, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. M. D. L. Ruiz, Y. H. Lim, and J. Zheng, “Adenosine A2A receptor as a drug discovery target,” Journal of Medicinal Chemistry, vol. 57, no. 9, pp. 3623–3650, 2014. View at Publisher · View at Google Scholar
  52. P. J. Gebicke-Haerter, F. Christoffel, J. Timmer, H. Northoff, M. Berger, and D. Van Calker, “Both adenosine A1- and A2-receptors are required to stimulate microglial proliferation,” Neurochemistry International, vol. 29, no. 1, pp. 37–42, 1996. View at Publisher · View at Google Scholar · View at Scopus
  53. K. Biber, K.-N. Klotz, M. Berger, P. J. Gebicke-Härter, and D. Van Calker, “Adenosine A1 receptor-mediated activation of phospholipase C in cultured astrocytes depends on the level of receptor expression,” Journal of Neuroscience, vol. 17, no. 13, pp. 4956–4964, 1997. View at Google Scholar · View at Scopus
  54. T. Othman, H. Yan, and S. A. Rivkees, “Oligodendrocytes express functional A1 adenosine receptors that stimulate cellular migration,” Glia, vol. 44, no. 2, pp. 166–172, 2003. View at Publisher · View at Google Scholar · View at Scopus
  55. P. B. Hansen and J. Schnermann, “Vasoconstrictor and vasodilator effects of adenosine in the kidney,” American Journal of Physiology - Renal Physiology, vol. 285, no. 4, pp. F590–F599, 2003. View at Publisher · View at Google Scholar · View at Scopus
  56. P. B. Hansen, H. Castrop, J. Briggs, and J. Schnermann, “Adenosine induces vasoconstriction through Gi-dependent activation of phospholipase C in isolated perfused afferent arterioles of mice,” Journal of the American Society of Nephrology, vol. 14, no. 10, pp. 2457–2465, 2003. View at Publisher · View at Google Scholar · View at Scopus
  57. D. Preti, P. G. Baraldi, A. R. Moorman, P. A. Borea, and K. Varani, “History and perspectives of A2A adenosine receptor antagonists as potential therapeutic agents,” Medicinal Research Reviews, vol. 35, no. 4, pp. 790–848, 2015. View at Publisher · View at Google Scholar · View at Scopus
  58. S. Sheth, R. Brito, D. Mukherjea, L. P. Rybak, and V. Ramkumar, “Adenosine receptors: Expression, function and regulation,” International Journal of Molecular Sciences, vol. 15, no. 2, pp. 2024–2052, 2014. View at Publisher · View at Google Scholar · View at Scopus
  59. S. Ferré, R. Baler, M. Bouvier et al., “Building a new conceptual framework for receptor heteromers,” Nature Chemical Biology, vol. 5, no. 3, pp. 131–134, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. F. Ciruela, V. Casadó, J. Mallol, E. I. Canela, C. Lluis, and R. Franco, “Immunological identification of A1 adenosine receptors in brain cortex,” Journal of Neuroscience Research, vol. 42, no. 6, pp. 818–828, 1995. View at Publisher · View at Google Scholar · View at Scopus
  61. K. Namba, T. Suzuki, and H. Nakata, “Immunogold electron microscopic evidence of in situ formation of homo- and heteromeric purinergic adenosine A1 and P2Y2 receptors in rat brain,” BMC Research Notes, vol. 3, p. 323, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Canals, J. Burgueño, D. Marcellino et al., “Homodimerization of adenosine A2A receptors: Qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer,” Journal of Neurochemistry, vol. 88, no. 3, pp. 726–734, 2004. View at Publisher · View at Google Scholar · View at Scopus
  63. F. Ciruela, V. Casadó, R. J. Rodrigues et al., “Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers,” Journal of Neuroscience, vol. 26, no. 7, pp. 2080–2087, 2006. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Cristóvão-Ferreira, G. Navarro, M. Brugarolas et al., “A1R-A2AR heteromers coupled to Gs and Gi/0 proteins modulate GABA transport into astrocytes,” Purinergic Signalling, vol. 9, no. 3, pp. 433–449, 2013. View at Publisher · View at Google Scholar · View at Scopus
  65. B. Johansson, L. Halldner, T. V. Dunwiddie et al., “Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 16, pp. 9407–9412, 2001. View at Publisher · View at Google Scholar · View at Scopus
  66. A. J. Hutchison, R. L. Webb, H. H. Oei, G. R. Ghai, M. B. Zimmerman, and M. Williams, “CGS 21680C, an A2 selective adenosine receptor agonist with preferential hypotensive activity,” Journal of Pharmacology and Experimental Therapeutics, vol. 251, no. 1, pp. 47–55, 1989. View at Google Scholar
  67. N. Dale and B. G. Frenguelli, “Release of adenosine and ATP during ischemia and epilepsy,” Current Neuropharmacology, vol. 7, no. 3, pp. 160–179, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. M. R. Blackburn, “Too much of a good thing: Adenosine overload in adenosine-deaminase-deficient mice,” Trends in Pharmacological Sciences, vol. 24, no. 2, pp. 66–70, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Ham and B. A. J. Evans, “An emerging role for adenosine and its receptors in bone homeostasis,” Frontiers in Endocrinology, vol. 3, p. 113, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. J. Wen and Y. Xia, “Adenosine signaling: Good or bad in erectile function?” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 4, pp. 845–850, 2012. View at Publisher · View at Google Scholar · View at Scopus
  71. M. Ohta, K. Toyama, D. D. Gutterman et al., “Ecto-5′-nucleotidase, CD73, is an endothelium-derived hyperpolarizing factor synthase,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, no. 3, pp. 629–636, 2013. View at Publisher · View at Google Scholar · View at Scopus
  72. M. A. Carroll, A. B. Doumad, J. Li, M. K. Cheng, J. R. Falck, and J. C. McGiff, “Adenosine 2A receptor vasodilation of rat preglomerular microvessels is mediated by EETs that activate the cAMP/PKA pathway,” American Journal of Physiology - Renal Physiology, vol. 291, no. 1, pp. F155–F161, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. M.-G. Feng and L. G. Navar, “Afferent arteriolar vasodilator effect of adenosine predominantly involves adenosine A2B receptor activation,” American Journal of Physiology - Renal Physiology, vol. 299, no. 2, pp. F310–F315, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. T. W. Hein, L. Belardinelli, and L. Kuo, “Adenosine A(2A) receptors mediate coronary microvascular dilation to adenosine: role of nitric oxide and ATP-sensitive potassium channels,” Journal of Pharmacology and Experimental Therapeutics, vol. 291, no. 2, pp. 655–664, 1999. View at Google Scholar · View at Scopus
  75. D. S. Ponnoth, M. S. Sanjani, C. Ledent, K. Roush, T. Krahn, and S. J. Mustafa, “Absence of adenosine-mediated aortic relaxation in A2A adenosine receptor knockout mice,” American Journal of Physiology - Heart and Circulatory Physiology, vol. 297, no. 5, pp. H1655–H1660, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. I. Pradhan, D. C. Zeldin, C. Ledent, J. S. Mustafa, J. R. Falck, and M. A. Nayeem, “High salt diet exacerbates vascular contraction in the absence of adenosine A2A receptor,” Journal of Cardiovascular Pharmacology, vol. 63, no. 5, pp. 385–394, 2014. View at Publisher · View at Google Scholar · View at Scopus
  77. A. Arsyad and G. P. Dobson, “Adenosine relaxation in isolated rat aortic rings and possible roles of smooth muscle Kv channels, KATP channels and A2a receptors,” BMC Pharmacology Toxicology, vol. 17, p. 23, 2016. View at Publisher · View at Google Scholar
  78. M. K. Cheng, A. B. Doumad, H. Jiang, J. R. Falck, J. C. McGiff, and M. A. Carroll, “Epoxyeicosatrienoic acids mediate adenosine-induced vasodilation in rat preglomerular microvessels (PGMV) via A2A receptors,” British Journal of Pharmacology, vol. 141, no. 3, pp. 441–448, 2004. View at Publisher · View at Google Scholar · View at Scopus
  79. O. Frøbert, G. Haink, U. Simonsen, C. H. Gravholt, M. Levin, and A. Deussen, “Adenosine concentration in the porcine coronary artery wall and A2A receptor involvement in hypoxia-induced vasodilatation,” Journal of Physiology, vol. 570, no. 2, pp. 375–384, 2006. View at Publisher · View at Google Scholar · View at Scopus
  80. T. W. Hein, Z. Yuan, R. H. Rosa Jr., and L. Kuo, “Requisite roles of A2A receptors, nitric oxide, and KATP channels in retinal arteriolar dilation in response to adenosine,” Investigative Ophthalmology and Visual Science, vol. 46, no. 6, pp. 2113–2119, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. H. Ohata, S. Cao, and R. C. Koehler, “Contribution of adenosine A2A and A2B receptors and heme oxygenase to AMPA-induced dilation of pial arterioles in rats,” American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol. 291, no. 3, pp. R728–R735, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. M. Radenkovic, L. Grbovic, S. Pesic, and D. Stojic, “Isolated rat inferior mesenteric artery response to adenosine: possible participation of Na+/K+-ATPase and potassium channels,” Pharmacological Reports, vol. 57, no. 6, pp. 824–832, 2005. View at Google Scholar
  83. A. Sato, K. Terata, H. Miura et al., “Mechanism of vasodilation to adenosine in coronary arterioles from patients with heart disease,” American Journal of Physiology - Heart and Circulatory Physiology, vol. 288, no. 4, pp. H1633–H1640, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. W. Abebe, S. R. Makujina, and S. J. Mustafa, “Adenosine receptor-mediated relaxation of porcine coronary artery in presence and absence of endothelium,” American Journal of Physiology, vol. 266, no. 5 Pt 2, pp. H2018–H2025, 1994. View at Google Scholar · View at Scopus
  85. S. J. Mustafa and A. O. Askar, “Evidence suggesting an Ra-type adenosine receptor in bovine coronary arteries,” Journal of Pharmacology and Experimental Therapeutics, vol. 232, no. 1, pp. 49–56, 1985. View at Google Scholar
  86. S. J. Mustafa, R. R. Morrison, B. Teng, and A. Pelleg, “Adenosine receptors and the heart: Role in regulation of coronary blood flow and cardiac electrophysiology,” Handbook of Experimental Pharmacology, vol. 193, pp. 161–188, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. V. Ralevic and G. Burnstock, “Receptors for purines and pyrimidines,” Pharmacological Reviews, vol. 50, no. 3, pp. 413–492, 1998. View at Google Scholar · View at Scopus
  88. M. V. Ramagopal, R. W. Chitwood Jr., and S. Jamal Mustafa, “Evidence for an A2 adenosine receptor in human coronary arteries,” European Journal of Pharmacology, vol. 151, no. 3, pp. 483–486, 1988. View at Publisher · View at Google Scholar · View at Scopus
  89. E. L. Liclican, J. C. McGiff, P. L. Pedraza, N. R. Ferreri, J. R. Falck, and M. A. Carroll, “Exaggerated response to adenosine in kidneys from high salt-fed rats: Role of epoxyeicosatrienoic acids,” American Journal of Physiology - Renal Physiology, vol. 289, no. 2, pp. F386–F392, 2005. View at Publisher · View at Google Scholar · View at Scopus
  90. I. Fleming, “Cytochrome p450 and vascular homeostasis,” Circulation Research, vol. 89, no. 9, pp. 753–762, 2001. View at Publisher · View at Google Scholar · View at Scopus
  91. Y. Ishibashi, D. J. Duncker, J. Zhang, and R. J. Bache, “ATP-sensitive K+ channels, adenosine, and nitric oxide-mediated mechanisms account for coronary vasodilation during exercise,” Circulation Research, vol. 82, no. 3, pp. 346–359, 1998. View at Publisher · View at Google Scholar · View at Scopus
  92. D. Ye, W. Zhou, T. Lu, S. G. Jagadeesh, J. R. Falck, and H.-C. Lee, “Mechanism of rat mesenteric arterial KATP channel activation by 14,15-epoxyeicosatrienoic acid,” American Journal of Physiology - Heart and Circulatory Physiology, vol. 290, no. 4, pp. H1326–H1336, 2006. View at Publisher · View at Google Scholar · View at Scopus
  93. L. Kuo and J. D. Chancellor, “Adenosine potentiates flow-induced dilation of coronary arterioles by activating KATP channels in endothelium,” American Journal of Physiology: Heart and Circulatory Physiology, vol. 269, no. 2, pp. H541–H549, 1995. View at Google Scholar · View at Scopus
  94. V. N. Mutafova-Yambolieva and K. D. Keef, “Adenosine-induced hyperpolarization in guinea pig coronary artery involves A2b receptors and KATP channels,” American Journal of Physiology, vol. 273, no. 6 Pt 2, pp. H2687–H2695, 1997. View at Google Scholar · View at Scopus
  95. D. S. Ponnoth, M. A. Nayeem, S. L. Tilley, C. Ledent, and S. Jamal Mustafa, “CYP-epoxygenases contribute to A2A receptor-mediated aortic relaxation via sarcolemmal KATP channels,” American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol. 303, no. 10, pp. R1003–R1010, 2012. View at Publisher · View at Google Scholar · View at Scopus
  96. Y. Cheng, J. F. Ndisang, G. Tang, K. Cao, and R. Wang, “Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats,” American Journal of Physiology: Heart and Circulatory Physiology, vol. 287, no. 5, pp. H2316–H2323, 2004. View at Publisher · View at Google Scholar · View at Scopus
  97. C. L. Heaps and D. K. Bowles, “Gender-specific K(+)-channel contribution to adenosine-induced relaxation in coronary arterioles,” Journal of Applied Physiology, vol. 92, no. 2, pp. 550–558, 2002. View at Publisher · View at Google Scholar · View at Scopus
  98. B. K. Kemp and T. M. Cocks, “Adenosine mediates relaxation of human small resistance-like coronary arteries via A2B receptors,” British Journal of Pharmacology, vol. 126, no. 8, pp. 1796–1800, 1999. View at Publisher · View at Google Scholar · View at Scopus
  99. Q. Li and D. G. Puro, “Adenosine activates ATP-sensitive K+ currents in pericytes of rat retinal microvessels: Role of A1 and A2a receptors,” Brain Research, vol. 907, no. 1-2, pp. 93–99, 2001. View at Publisher · View at Google Scholar · View at Scopus
  100. H. A. Olanrewaju, B. S. Gafurov, and E. M. Lieberman, “Involvement of K+ channels in adenosine A2A and A2B receptor-mediated hyperpolarization of porcine coronary artery endothelial cells,” Journal of Cardiovascular Pharmacology, vol. 40, no. 1, pp. 43–49, 2002. View at Publisher · View at Google Scholar · View at Scopus
  101. B. C. Sheridan, R. C. McIntyre Jr, D. R. Meldrum, and D. A. Fullerton, “KATP channels contribute to beta- and adenosine receptor-mediated pulmonary vasorelaxation,” American Journal of Physiology, vol. 273, no. 5 Pt 1, pp. L950–L956, 1997. View at Google Scholar
  102. L. Tang, M. Parker, Q. Fei, and R. Loutzenhiser, “Afferent arteriolar adenosine A2a receptors are coupled to KATP in in vitro perfused hydronephrotic rat kidney,” American Journal of Physiology, vol. 277, no. 6 Pt 2, pp. F926–F933, 1999. View at Google Scholar · View at Scopus
  103. D. Ye, W. Zhou, and H.-C. Lee, “Activation of rat mesenteric arterial KATP channels by 11,12-epoxyeicosatrienoic acid,” American Journal of Physiology - Heart and Circulatory Physiology, vol. 288, no. 1, pp. H358–H364, 2005. View at Publisher · View at Google Scholar · View at Scopus
  104. T. Lu, D. Ye, X. Wang et al., “Cardiac and vascular KATP channels in rats are activated by endogenous epoxyeicosatrienoic acids through different mechanisms,” Journal of Physiology, vol. 575, no. 2, pp. 627–644, 2006. View at Publisher · View at Google Scholar · View at Scopus
  105. D. S. Ponnoth, M. A. Nayeem, S. S. Kunduri et al., “Role of omega-hydroxylase in adenosine-mediated aortic response through MAP kinase using A2A-receptor knockout mice,” American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol. 302, no. 4, pp. R400–R408, 2012. View at Publisher · View at Google Scholar · View at Scopus
  106. A. Eisenstein and K. Ravid, “G Protein-coupled receptors and adipogenesis: A focus on adenosine receptors,” Journal of Cellular Physiology, vol. 229, no. 4, pp. 414–421, 2014. View at Publisher · View at Google Scholar · View at Scopus
  107. H. R. Ansari, B. Teng, A. Nadeem et al., “A(1) adenosine receptor-mediated PKC and p42/p44 MAPK signaling in mouse coronary artery smooth muscle cells,” American Journal of Physiology - Heart and Circulatory Physiology, vol. 297, no. 3, pp. H1032–H1039, 2009. View at Publisher · View at Google Scholar · View at Scopus
  108. “Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group,” BMJ, vol. 297, no. 6644, pp. 319–328, 1988. View at Publisher · View at Google Scholar
  109. K. T. Khaw, S. Bingham, A. Welch et al., “Blood pressure and urinary sodium in men and women: the Norfolk Cohort of the European prospective investigation into cancer (EPIC-Norfolk),” The American Journal of Clinical Nutrition, vol. 80, no. 5, pp. 1397–1403, 2004. View at Google Scholar · View at Scopus
  110. E. L. Liclican, J. C. McGiff, J. R. Falck, and M. A. Carroll, “Failure to upregulate the adenosine 2A receptor-epoxyeicosatrienoic acid pathway contributes to the development of hypertension in Dahl salt-sensitive rats,” American Journal of Physiology - Renal Physiology, vol. 295, no. 6, pp. F1696–F1704, 2008. View at Publisher · View at Google Scholar · View at Scopus
  111. H. M. Siragy and J. Linden, “Sodium intake markedly alters renal interstitial fluid adenosine,” Hypertension, vol. 27, no. 3 Pt 1, pp. 404–407, 1996. View at Publisher · View at Google Scholar · View at Scopus
  112. A.-P. Zou, F. Wu, P.-L. Li, and A. W. Cowley Jr., “Effect of chronic salt loading on adenosine metabolism and receptor expression in renal cortex and medulla in rats,” Hypertension, vol. 33, no. 1 Pt 2, pp. 511–516, 1999. View at Publisher · View at Google Scholar · View at Scopus
  113. H. Andersen, M. G. Jaff, D. Høgh, P. Vanhoutte, and P. B. Hansen, “Adenosine elicits an eNOS-independent reduction in arterial blood pressure in conscious mice that involves adenosine A2A receptors,” Acta Physiologica, vol. 203, no. 1, pp. 197–207, 2011. View at Publisher · View at Google Scholar · View at Scopus
  114. D. R. Harder, W. B. Campbell, and R. J. Roman, “Role of cytochrome p-450 enzymes and metabolites of arachidonic acid in the control of vascular tone,” Journal of Vascular Research, vol. 32, no. 2, pp. 79–92, 1995. View at Publisher · View at Google Scholar · View at Scopus
  115. L. Lapuerta, N. Chacos, J. R. Falck, H. Jacobson, and J. H. Capdevila, “Renal microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid,” American Journal of the Medical Sciences, vol. 295, no. 4, pp. 275–279, 1988. View at Publisher · View at Google Scholar · View at Scopus
  116. K. G. Proctor, J. R. Falck, and J. Capdevila, “Intestinal vasodilation by epoxyeicosatrienoic acids: Arachidonic acid metabolites produced by a cytochrome P450 monooxygenase,” Circulation Research, vol. 60, no. 1, pp. 50–59, 1987. View at Publisher · View at Google Scholar · View at Scopus
  117. Y. H. Ma, D. R. Harder, J. E. Clark, and R. J. Roman, “Effects of 12-HETE on isolated dog renal arcuate arteries,” American Journal of Physiology, vol. 261, no. 2 Pt 2, pp. H451–456, 1991. View at Google Scholar
  118. W. B. Campbell, D. Gebremedhin, P. F. Pratt, and D. R. Harder, “Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors,” Circulation Research, vol. 78, no. 3, pp. 415–423, 1996. View at Publisher · View at Google Scholar · View at Scopus
  119. I. Fleming, “The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease,” Pharmacological Reviews, vol. 66, no. 4, pp. 1106–1140, 2014. View at Publisher · View at Google Scholar · View at Scopus
  120. J. Seubert, B. Yang, J. A. Bradbury et al., “Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway,” Circulation Research, vol. 95, no. 5, pp. 506–514, 2004. View at Publisher · View at Google Scholar · View at Scopus
  121. D. Gebremedhin, Y. H. Ma, J. R. Falck, R. J. Roman, M. VanRollins, and D. R. Harder, “Mechanism of action of cerebral epoxyeicosatrienoic acids on cerebral arterial smooth muscle,” American Journal of Physiology, vol. 263, no. 2 Pt 2, pp. H519–H525, 1992. View at Google Scholar · View at Scopus
  122. J. D. Imig, L. G. Navar, R. J. Roman, K. K. Reddy, and J. R. Falck, “Actions of epoxygenase metabolites on the preglomerular vasculature,” Journal of the American Society of Nephrology, vol. 7, no. 11, pp. 2364–2370, 1996. View at Google Scholar · View at Scopus
  123. C. J. Sinal, M. Miyata, M. Tohkin, K. Nagata, J. R. Bend, and F. J. Gonzalez, “Targeted disruption of soluble epoxide hydrolase reveals a role in blood pressure regulation,” Journal of Biological Chemistry, vol. 275, no. 51, pp. 40504–40510, 2000. View at Publisher · View at Google Scholar · View at Scopus
  124. A. Hanif, M. L. Edin, D. C. Zeldin, C. Morisseau, and M. A. Nayeem, “Effect of soluble epoxide hydrolase on the modulation of coronary reactive hyperemia: Role of oxylipins and PPARγ,” PLoS ONE, vol. 11, no. 9, article 0162147, 2016. View at Publisher · View at Google Scholar · View at Scopus
  125. K. M. Gauthier, C. Deeter, U. M. Krishna et al., “14,15-Epoxyeicosa-5(Z)-enoic acid: A selective epoxyeicosatrienoic acid antagonist that inhibits endothelium-dependent hyperpolarization and relaxation in coronary arteries,” Circulation Research, vol. 90, no. 9, pp. 1028–1036, 2002. View at Publisher · View at Google Scholar · View at Scopus
  126. Y. Liu, Y. Zhu, F. Rannou et al., “Laminar flow activates peroxisome proliferator-activated receptor-γ in vascular endothelial cells,” Circulation, vol. 110, no. 9, pp. 1128–1133, 2004. View at Publisher · View at Google Scholar · View at Scopus
  127. J. D. Coffman and D. E. Gregg, “Reactive hyperemia characteristics of the myocardium,” The American journal of physiology, vol. 199, pp. 1143–1149, 1960. View at Google Scholar · View at Scopus
  128. M. P. Kingsbury, M. A. Turner, N. A. Flores, E. Bovill, and D. J. Sheridan, “Endogenous and exogenous coronary vasodilatation are attenuated in cardiac hypertrophy: A morphological defect?” Journal of Molecular and Cellular Cardiology, vol. 32, no. 3, pp. 527–538, 2000. View at Publisher · View at Google Scholar · View at Scopus
  129. I. Pradhan, C. Ledent, S. J. Mustafa, C. Morisseau, and M. A. Nayeem, “High salt diet modulates vascular response in A(2A)AR(+/+) and A(2A)AR(−/−) mice: role of sEH, PPARγ, and K(ATP) channels,” Molecular and Cellular Biochemistry, vol. 404, no. 1-2, pp. 87–96, 2015. View at Publisher · View at Google Scholar · View at Scopus
  130. G. Chinetti, J.-C. Fruchart, and B. Staels, “Peroxisome proliferator-activated receptors (PPARs): nuclear receptors with functions in the vascular wall,” Zeitschrift fur Kardiologie, vol. 90, 3, pp. 125–132, 2001. View at Publisher · View at Google Scholar · View at Scopus
  131. W. A. Hsueh, S. Jackson, and R. E. Law, “Control of vascular cell proliferation and migration by PPAR-γ: A new approach to the macrovascular complications of diabetes,” Diabetes Care, vol. 24, no. 2, pp. 392–397, 2001. View at Publisher · View at Google Scholar · View at Scopus
  132. S. W. Seto, T. Y. Lam, G. P. H. Leung et al., “Comparison of vascular relaxation, lipolysis and glucose uptake by peroxisome proliferator-activated receptor-γ activation in + db/+ m and + db/+ db mice,” European Journal of Pharmacology, vol. 572, no. 1, pp. 40–48, 2007. View at Publisher · View at Google Scholar · View at Scopus
  133. M. J. Ryan, S. P. Didion, S. Mathur, F. M. Faraci, and C. D. Sigmund, “PPARγ Agonist Rosiglitazone Improves Vascular Function and Lowers Blood Pressure in Hypertensive Transgenic Mice,” Hypertension, vol. 43, no. 3, pp. 661–666, 2004. View at Publisher · View at Google Scholar · View at Scopus
  134. Z. Cai, G. Zhao, J. Yan et al., “CYP2J2 overexpression increases EETs and protects against angiotensin II-induced abdominal aortic aneurysm in mice,” Journal of Lipid Research, vol. 54, no. 5, pp. 1448–1456, 2013. View at Publisher · View at Google Scholar · View at Scopus
  135. L. Ashley Cowart, S. Wei, M.-H. Hsu et al., “The CYP4A isoforms hydroxylate epoxyeicosatrienoic acids to form high affinity peroxisome proliferator-activated receptor ligands,” Journal of Biological Chemistry, vol. 277, no. 38, pp. 35105–35112, 2002. View at Publisher · View at Google Scholar · View at Scopus
  136. Y. Liu, Y. Zhang, K. Schmelzer et al., “The antiinflammatory effect of laminar flow: The role of PPARγ, epoxyeicosatrienoic acids, and soluble epoxide hydrolase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 46, pp. 16747–16752, 2005. View at Publisher · View at Google Scholar · View at Scopus