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International Journal of Hypertension
Volume 2012, Article ID 915057, 10 pages
http://dx.doi.org/10.1155/2012/915057
Review Article

Biochemical and Molecular Aspects of Vascular Adrenergic Regulation of Blood Pressure in the Elderly

William E. Schutzer and Scott L. Mader

Portland VA Medical Center and Research Service—RD 26, Oregon Health and Science University School of Medicine, P.O. Box 1034, Portland, OR 97201, USA

Received 14 July 2011; Accepted 28 July 2011

Academic Editor: Blas Gil Extremera

Copyright © 2012 William E. Schutzer and Scott L. Mader. 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. K. Humes, “The population 65 years and older: aging in America,” in US Department of Comerce, Economics and Statistics Administration. The Book of the States 2005, pp. 464–468, The Council of State Governents, 2005. View at Google Scholar
  2. E. G. Lakatta, M. Wang, and S. S. Najjar, “Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels,” Medical Clinics of North America, vol. 93, no. 3, pp. 583–604, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. M. A. Lim and R. R. Townsend, “Arterial compliance in the elderly: its effect on blood pressure measurement and cardiovascular outcomes,” Clinics in Geriatric Medicine, vol. 25, no. 2, pp. 191–205, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. M. D. Herrera, C. Mingorance, R. Rodríguez-Rodríguez, and M. Alvarez de Sotomayor, “Endothelial dysfunction and aging: an update,” Ageing Research Reviews, vol. 9, no. 2, pp. 142–152, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. A. Orlandi, M. L. Bochaton-Piallat, G. Gabbiani, and L. G. Spagnoli, “Aging, smooth muscle cells and vascular pathobiology: implications for atherosclerosis,” Atherosclerosis, vol. 188, no. 2, pp. 221–230, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. C. Dessy and J. L. Balligand, “Beta3-adrenergic receptors in cardiac and vascular tissues emerging concepts and therapeutic perspectives,” Advances in Pharmacology, vol. 59, no. C, pp. 135–163, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. J. Chapman, W. E. Schutzer, V. J. Watts, and S. L. Mader, “Impaired cholera toxin relaxation with age in rat aorta,” Journals of Gerontology—Series A, vol. 54, no. 4, pp. B154–B159, 1999. View at Google Scholar · View at Scopus
  8. B. K. Kobilka, “Structural insights into adrenergic receptor function and pharmacology,” Trends in Pharmacological Sciences, vol. 32, no. 4, pp. 213–218, 2011. View at Google Scholar
  9. J. L. Fleg, W. S. Aronow, and W. H. Frishman, “Cardiovascular drug therapy in the elderly: benefits and challenges,” Nature Reviews Cardiology, vol. 8, no. 1, pp. 13–28, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. R. J. Lefkowitz, “Seven transmembrane receptors: something old, something new,” Acta Physiologica, vol. 190, no. 1, pp. 9–19, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. M. A. Gaballa, A. D. Eckhart, W. J. Koch, and S. Goldman, “Vascular β-adrenergic receptor adenylyl cyclase system in maturation and aging,” Journal of Molecular and Cellular Cardiology, vol. 32, no. 9, pp. 1745–1755, 2000. View at Publisher · View at Google Scholar · View at Scopus
  12. W. E. Schutzer, H. Xue, J. F. Reed et al., “Effect of age on vascular beta2-adrenergic receptor desensitization is not mediated by the receptor coupling to Galphai proteins,” Journals of Gerontology—Series A, vol. 61, no. 9, pp. 899–906, 2006. View at Google Scholar
  13. M. P. Walsh, “Regulation of vascular smooth muscle tone,” Canadian Journal of Physiology and Pharmacology, vol. 72, no. 8, pp. 919–936, 1994. View at Google Scholar · View at Scopus
  14. D. R. Hathaway, K. L. March, J. A. Lash, L. P. Adam, and R. L. Wilensky, “Vascular smooth muscle. A review of the molecular basis of contractility,” Circulation, vol. 83, no. 2, pp. 382–390, 1991. View at Google Scholar · View at Scopus
  15. A. P. Somlyo, X. Wu, L. A. Walker, and A. V. Somlyo, “Pharmacomechanical coupling: the role of calcium, G-proteins, kinases, and phosphatases,” Reviews of Physiology, Biochemistry and Pharmacology, vol. 134, pp. 201–234, 1999. View at Google Scholar · View at Scopus
  16. E. M. Ross, “Pharmacodynamics,” in Goodman and Gilman's The Pharmacological Basis of Therapeutics, J. G. Hardman et al., Ed., pp. 29–42, McGraw-Hill, New York, NY, USA, 1996. View at Google Scholar
  17. J. J. C. Michel and J. D. Scott, “AKAP-mediated signal transduction,” Annual Review of Pharmacology and Toxicology, vol. 42, pp. 235–257, 2002. View at Publisher · View at Google Scholar · View at Scopus
  18. J. L. Benovic, R. H. Strasser, M. G. Caron, and R. J. Lefkowitz, “β-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 9, pp. 2797–2801, 1986. View at Google Scholar · View at Scopus
  19. W. E. Miller and R. J. Lefkowitz, “Expanding roles for β-arrestins as scaffolds and adaptors in G protein-coupled receptor signaling and trafficking,” Current Opinion in Cell Biology, pp. 139–145, 2001. View at Google Scholar
  20. S. Guimarães and D. Moura, “Vascular adenoreceptors: an update,” Pharmacological Reviews, vol. 53, no. 2, pp. 319–356, 2001. View at Google Scholar · View at Scopus
  21. J. H. Hurley, “Structure, mechanism, and regulation of mammalian adenylyl cyclase,” Journal of Biological Chemistry, vol. 274, no. 12, pp. 7599–7602, 1999. View at Publisher · View at Google Scholar · View at Scopus
  22. R. K. Sunahara, C. W. Dessauer, and A. G. Gilman, “Complexity and diversity of mammalian adenylyl cyclases,” Annual Review of Pharmacology and Toxicology, vol. 36, pp. 461–480, 1996. View at Google Scholar · View at Scopus
  23. J. A. Pitcher, N. J. Freedman, and R. J. Lefkowitz, “G protein-coupled receptor kinases,” Annual Review of Biochemistry, vol. 67, pp. 653–692, 1998. View at Publisher · View at Google Scholar · View at Scopus
  24. J. G. Krupnick and J. L. Benovic, “The role of receptor kinases and arrestins in G-protein-coupled receptor regulation,” Annual Review of Pharmacology and Toxicology, vol. 38, pp. 289–319, 1998. View at Google Scholar · View at Scopus
  25. M. Colledge and J. D. Scott, “AKAPs: from structure to function,” Trends in Cell Biology, vol. 9, no. 6, pp. 216–221, 1999. View at Publisher · View at Google Scholar · View at Scopus
  26. B. Zheng, Y. C. Ma, R. S. Ostrom et al., “RGS-PX1, a GAP for Gαs and sorting nexin in vesicular trafficking,” Science, vol. 294, no. 5548, pp. 1939–1942, 2001. View at Publisher · View at Google Scholar · View at Scopus
  27. J. H. Fleisch, “Further studies on the effect of ageing on β-adrenoceptor activity of rat aorta,” The British Journal of Pharmacology, vol. 42, no. 2, pp. 311–313, 1971. View at Google Scholar · View at Scopus
  28. J. H. Fleisch, H. M. Maling, and B. B. Brodie, “Beta receptor activity in aorta: variations with age and species,” Circulation Research, vol. 26, no. 2, pp. 151–162, 1970. View at Google Scholar · View at Scopus
  29. J. H. Fleisch, “Age-related decrease in beta adrenoceptor activity of the cardiovascular system,” Trends in Pharmacological Sciences, vol. 2, no. C, pp. 337–339, 1981. View at Google Scholar · View at Scopus
  30. D. M. Rosenbaum, C. Zhang, J. A. Lyons et al., “Structure and function of an irreversible agonist-beta(2) adrenoceptor complex,” Nature, vol. 469, no. 7329, pp. 236–240, 2011. View at Google Scholar
  31. R. Begonha, D. Moura, and S. Guimaraes, “Vascular β-adrenoceptor-mediated vasorelaxation and tone of the tissues of the canine artery,” Journal of Pharmacy and Pharmacology, vol. 47, no. 6, pp. 510–513, 1995. View at Google Scholar · View at Scopus
  32. W. Osswald and S. Guimarães, “Adrenergic mechanisms in blood vessels: morphological and pharmacological aspects,” Reviews of Physiology Biochemistry and Pharmacology, vol. 96, pp. 53–122, 1983. View at Google Scholar · View at Scopus
  33. A. J. Chruscinski, D. K. Rohrer, E. Schauble, K. H. Desai, D. Bernstein, and B. K. Kobilka, “Targeted disruption of the β2 adrenergic receptor gene,” Journal of Biological Chemistry, vol. 274, no. 24, pp. 16694–16700, 1999. View at Publisher · View at Google Scholar · View at Scopus
  34. D. K. Rohrer, A. Chruscinski, E. H. Schauble, D. Bernstein, and B. K. Kobilka, “Cardiovascular and metabolic alterations in mice lacking both β1- and β2-adrenergic receptors,” Journal of Biological Chemistry, vol. 274, no. 24, pp. 16701–16708, 1999. View at Publisher · View at Google Scholar · View at Scopus
  35. R. P. Xiao, H. Cheng, Y. Y. Zhou, M. Kuschel, and E. G. Lakatta, “Recent advances in cardiac β2-adrenergic signal transduction,” Circulation Research, vol. 85, no. 11, pp. 1092–1100, 1999. View at Google Scholar · View at Scopus
  36. N. J. Freedman, S. B. Liggett, D. E. Drachman, G. Pei, M. G. Caron, and R. J. Lefkowitz, “Phosphorylation and desensitization of the human β1-adrenergic receptor. Involvement of G protein-coupled receptor kinases and cAMP-dependent protein kinase,” Journal of Biological Chemistry, vol. 270, no. 30, pp. 17953–17961, 1995. View at Publisher · View at Google Scholar · View at Scopus
  37. W. P. Hausdorff, M. Bouvier, B. F. O'Dowd, G. P. Irons, M. G. Caron, and R. J. Lefkowitz, “Phosphorylation sites on two domains of the β2-adrenergic receptor are involved in distinct pathways of receptor desensitization,” Journal of Biological Chemistry, vol. 264, no. 21, pp. 12657–12665, 1989. View at Google Scholar · View at Scopus
  38. Y. Daaka, L. M. Luttrell, and R. J. Lefkowitz, “Switching of the coupling of the β2-adrenergic receptor to different G proteins by protein kinase A,” Nature, vol. 390, no. 6655, pp. 88–91, 1997. View at Publisher · View at Google Scholar · View at Scopus
  39. R. P. Xiao, “Beta-adrenergic signaling in the heart: dual coupling of the beta2-adrenergic receptor to G(s) and G(i) proteins,” Science's STKE, vol. 2001, no. 104, p. RE15, 2001. View at Google Scholar · View at Scopus
  40. R. J. Lefkowitz, K. L. Pierce, and L. M. Luttrell, “Dancing with different partners: protein kinase A phosphorylation of seven membrane-spanning receptors regulates their G protein-coupling specificity,” Molecular Pharmacology, vol. 62, no. 5, pp. 971–974, 2002. View at Publisher · View at Google Scholar · View at Scopus
  41. N. M. Tepe and S. B. Liggett, “Functional receptor coupling to G(i) is a mechanism of agonist-promoted desensitization of the β2-adrenergic receptor,” Journal of Receptor and Signal Transduction Research, vol. 20, no. 1, pp. 75–85, 2000. View at Google Scholar · View at Scopus
  42. S. B. Liggett, N. J. Freedman, D. A. Schwinn, and R. J. Lefkowitz, “Structural basis for receptor subtype-specific regulation revealed by a chimeric β3/β2-adrenergic receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 8, pp. 3665–3669, 1993. View at Google Scholar · View at Scopus
  43. R. P. Xiao, P. Avdonin, Y. Y. Zhou et al., “Coupling of β2-adrenoceptor to G(i) proteins and its physiological relevance in murine cardiac myocytes,” Circulation Research, vol. 84, no. 1, pp. 43–52, 1999. View at Google Scholar · View at Scopus
  44. Z. Chen, G. Miao, M. Liu et al., “Age-related up-regulation of β3-adrenergic receptor in heart-failure rats,” Journal of Receptors and Signal Transduction, vol. 30, no. 4, pp. 227–233, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. H. Gurdal, E. Friedman, and M. Johnson, “β-Adrenoceptor-G(αs) coupling decreases with age in rat aorta,” Molecular Pharmacology, vol. 47, no. 4, pp. 772–778, 1995. View at Google Scholar · View at Scopus
  46. J. F. Mercier, A. Salahpour, S. Angers, A. Breit, and M. Bouvier, “Quantitative assessment of β1- and β2-adrenergic receptor homo- and heterodimerization by bioluminescence resonance energy transfer,” Journal of Biological Chemistry, vol. 277, no. 47, pp. 44925–44931, 2002. View at Publisher · View at Google Scholar · View at Scopus
  47. C. Lavoie, J. F. Mercier, A. Salahpour et al., “β1/β2-adrenergic receptor heterodimerization regulates β2-adrenergic receptor internalization and ERK signaling efficacy,” Journal of Biological Chemistry, vol. 277, no. 38, pp. 35402–35410, 2002. View at Publisher · View at Google Scholar · View at Scopus
  48. W. Z. Zhu, K. Chakir, S. Zhang et al., “Heterodimerization of beta1- and beta2-adrenergic receptor subtypes optimizes beta-adrenergic modulation of cardiac contractility,” Circulation Research, vol. 97, no. 3, pp. 244–251, 2005. View at Google Scholar
  49. A. Ianoul, D. D. Grant, Y. Rouleau, M. Bani-Yaghoub, L. J. Johnston, and J. P. Pezacki, “Imaging nanometer domains of beta-adrenergic receptor complexes on the surface of cardiac myocytes,” Nature Chemical Biology, vol. 1, no. 4, pp. 196–202, 2005. View at Publisher · View at Google Scholar · View at Scopus
  50. T. J. LaRocca, M. Schwarzkopf, P. Altman et al., “Beta2-Adrenergic receptor signaling in the cardiac myocyte is modulated by interactions with CXCR4,” Journal of Cardiovascular Pharmacology, vol. 56, no. 5, pp. 548–559, 2011. View at Google Scholar
  51. W. E. Schutzer, J. F. Reed, M. Bliziotes, and S. L. Mader, “Upregulation of G protein-linked receptor kinases with advancing age in rat aorta,” The American Journal of Physiology, vol. 280, no. 3, pp. R897–R903, 2001. View at Google Scholar · View at Scopus
  52. M. D. Johnson, Y. Zhou, E. Friedman, and J. Roberts, “Expression of G protein α subunits in the aging cardiovascular system,” Journals of Gerontology—Series A, vol. 50, no. 1, pp. B14–B19, 1995. View at Google Scholar · View at Scopus
  53. M. G. Kazanietz and M. A. Enero, “Decreased β-adrenoceptor-mediated vasodilation in aorta from aged rats: possible involvement of a stimulatory GTP-binding protein,” European Journal of Pharmacology, vol. 198, no. 2-3, pp. 177–181, 1991. View at Google Scholar · View at Scopus
  54. S. L. Mader, C. L. Downing, J. Amos-Landgraf, and P. Swebjka, “Age-related changes in G proteins in rat aorta,” Journals of Gerontology—Series A, vol. 51, no. 2, pp. B111–B116, 1996. View at Google Scholar · View at Scopus
  55. W. E. Schutzer, V. J. Watts, J. Chapman et al., “Viral-mediated gene delivery of constitutively activated Gαs alters vasoreactivity,” Clinical and Experimental Pharmacology and Physiology, vol. 27, no. 1-2, pp. 9–13, 2000. View at Publisher · View at Google Scholar · View at Scopus
  56. J. Chen, M. DeVivo, J. Dingus et al., “A region of adenylyl cyclase 2 critical for regulation by G protein βγ subunits,” Science, vol. 268, no. 5214, pp. 1166–1169, 1995. View at Google Scholar · View at Scopus
  57. D. E. Clapham and E. J. Neer, “G protein beta gamma subunits,” Annual Review of Pharmacology and Toxicology, vol. 37, pp. 167–203, 1997. View at Google Scholar
  58. W. E. Schutzer and S. L. Mader, “Age-related changes in adrenergic signaling: clinical and mechanistic implications,” Ageing Research Reviews, vol. 2, no. 2, pp. 169–190, 2003. View at Publisher · View at Google Scholar · View at Scopus
  59. S. L. Mader and P. A. Alley, “Age-related changes in adenylyl cyclase activity in rat aorta membranes,” Mechanisms of Ageing & Development, vol. 101, no. 1-2, pp. 111–118, 1998. View at Google Scholar
  60. N. Defer, M. Best-Belpomme, and J. Hanoune, “Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase,” The American Journal of Physiology, vol. 279, no. 3, pp. F400–F416, 2000. View at Google Scholar · View at Scopus
  61. J. Zhang, M. Sato, E. Duzic, S. W. Kubalak, S. M. Lanier, and J. G. Webb, “Adenylyl cyclase isoforms and vasopressin enhancement of agonist-stimulated cAMP in vascular smooth muscle cells,” The American Journal of Physiology, vol. 273, no. 2, pp. H971–H980, 1997. View at Google Scholar · View at Scopus
  62. W. E. Schutzer, H. Xue, J. F. Reed, J. B. Roullet, S. Anderson, and S. L. Mader, “Angiotensin II enhances β-adrenergic receptor-mediated vasorelaxation in aorta from young but not old rats,” The American Journal of Physiology, vol. 279, no. 6, pp. H2807–H2814, 2000. View at Google Scholar · View at Scopus
  63. P. Schoeffter and J. C. Stoclet, “Age-related differences in cyclic AMP metabolism and their consequences on relaxation induced by isoproterenol and phosphodiesterase inhibitors in rat isolated aorta,” Mechanisms of Ageing and Development, vol. 54, no. 3, pp. 197–205, 1990. View at Publisher · View at Google Scholar · View at Scopus
  64. C. L. Miller and C. Yan, “Targeting cyclic nucleotide phosphodiesterase in the heart: therapeutic implications,” Journal of Cardiovascular Translational Research, vol. 3, no. 5, pp. 507–515, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. R. L. Elvebak, J. H. Eisenach, M. J. Joyner, and W. T. Nicholson, “The function of vascular smooth muscle phosphodiesterase III is preserved in healthy human aging,” Clinical and Translational Science, vol. 3, no. 5, pp. 239–242, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. M. J. Lohse, J. L. Benovic, J. Codina, M. G. Cargon, and R. J. Lefkowitz, “β-Arrestin: a protein that regulates β-adrenergic receptor function,” Science, vol. 248, no. 4962, pp. 1547–1550, 1990. View at Google Scholar · View at Scopus
  67. P. Sohlemann, M. Hekman, M. Puzicha, C. Buchen, and M. J. Lohse, “Binding of purified recombinant β-arrestin to guanine-nucleotide-binding-protein-coupled receptors,” European Journal of Biochemistry, vol. 232, no. 2, pp. 464–470, 1995. View at Publisher · View at Google Scholar · View at Scopus
  68. Z. L. Fredericks, J. A. Pitcher, and R. J. Lefkowitz, “Identification of the G protein-coupled receptor kinases phosphorylation sites in the human β-adrenergic receptor,” Journal of Biological Chemistry, vol. 271, no. 23, pp. 13796–13803, 1996. View at Google Scholar · View at Scopus
  69. M. Ungerer, M. Böhm, J. S. Elce, E. Erdmann, and M. J. Lohse, “Altered expression of β-adrenergic receptor kinase and β1-adrenergic receptors in the failing human heart,” Circulation, vol. 87, no. 2, pp. 454–463, 1993. View at Google Scholar · View at Scopus
  70. H. M. Huang and G. E. Gibson, “Altered β-adrenergic receptor-stimulated cAMP formation in cultured skin fibroblasts from Alzheimer donors,” Journal of Biological Chemistry, vol. 268, no. 20, pp. 14616–14621, 1993. View at Google Scholar · View at Scopus
  71. W. Schutzer, D. Beard, J. Reed et al., “Characterization of clonal vascular smooth muscle cell lines derived from young & old fischer 344 rats,” In Vitro Cellular & Developmental Biology—Animal, vol. 47, no. 7, pp. 445–450, 2011. View at Google Scholar
  72. A. D. Eckhart, T. Ozaki, H. Tevaearai, H. A. Rockman, and W. J. Koch, “Vascular-targeted overexpression of G protein-coupled receptor kinase-2 in transgenic mice attenuates β-adrenergic receptor signaling and increases resting blood pressure,” Molecular Pharmacology, vol. 61, no. 4, pp. 749–758, 2002. View at Publisher · View at Google Scholar · View at Scopus
  73. R. Gros, J. L. Benovic, C. M. Tan, and R. D. Feldman, “G-protein-coupled receptor kinase activity is increased in hypertension,” Journal of Clinical Investigation, vol. 99, no. 9, pp. 2087–2093, 1997. View at Google Scholar · View at Scopus
  74. L. Nogues, A. Salcedo, F. Mayor Jr. et al., “Multiple scaffolding functions of {beta}-arrestins in the degradation of G protein-coupled receptor kinase 2,” Journal of Biological Chemistry, vol. 286, no. 2, pp. 1165–1173, 2011. View at Google Scholar
  75. R. R. Neubig, “Membrane organization in G-protein mechanisms,” FASEB Journal, vol. 8, no. 12, pp. 939–946, 1994. View at Google Scholar · View at Scopus
  76. E. J. Smart, G. A. Graf, M. A. McNiven et al., “Caveolins, liquid-ordered domains, and signal transduction,” Molecular and Cellular Biology, vol. 19, no. 11, pp. 7289–7304, 1999. View at Google Scholar · View at Scopus
  77. N. Oka, K. Asai, R. K. Kudej et al., “Downregulation of caveolin by chronic β-adrenergic receptor stimulation in mice,” The American Journal of Physiology, vol. 273, no. 6, pp. C1957–C1962, 1997. View at Google Scholar · View at Scopus
  78. C. Schwencke, S. Okumura, M. Yamamoto, Y. J. Geng, and Y. Ishikawa, “Colocalization of β-adrenergic receptors and caveolin within the plasma membrane,” Journal of Cellular Biochemistry, vol. 75, no. 1, pp. 64–72, 1999. View at Google Scholar · View at Scopus
  79. S. Li, T. Okamoto, M. Chun et al., “Evidence for a regulated interaction between heterotrimeric G proteins and caveolin,” Journal of Biological Chemistry, vol. 270, no. 26, pp. 15693–15701, 1995. View at Publisher · View at Google Scholar · View at Scopus
  80. C. Schwencke, M. Yamamoto, S. Okumura, Y. Toya, S. J. Kim, and Y. Ishikawa, “Compartmentation of cyclic adenosine 3',5'-monophosphate signaling in caveolae,” Molecular Endocrinology, vol. 13, no. 7, pp. 1061–1070, 1999. View at Google Scholar · View at Scopus
  81. R. S. Ostrom, J. D. Violin, S. Coleman, and P. A. Insel, “Selective enhancement of β-adrenergic receptor signaling by overexpression of adenylyl cyclase type 6: colocalization of receptor and adenylyl cyclase in caveolae of cardiac myocytes,” Molecular Pharmacology, vol. 57, no. 5, pp. 1075–1079, 2000. View at Google Scholar · View at Scopus
  82. Y. Toya, C. Schwencke, J. Couet, M. P. Lisanti, and Y. Ishikawa, “Inhibition of adenylyl cyclase by caveolin peptides,” Endocrinology, vol. 139, no. 4, pp. 2025–2031, 1998. View at Google Scholar · View at Scopus
  83. C. V. Carman, M. P. Lisanti, and J. L. Benovic, “Regulation of G-protein receptor kinases by caveolin,” Journal of Biological Chemistry, vol. 274, no. 13, pp. 8858–8864, 1999. View at Publisher · View at Google Scholar · View at Scopus
  84. J. Kawabe, B. S. Grant, M. Yamamoto, C. Schwencke, S. Okumura, and Y. Ishikawa, “Changes in caveolin subtype protein expression in aging rat organs,” Molecular and Cellular Endocrinology, vol. 176, no. 1-2, pp. 91–95, 2001. View at Publisher · View at Google Scholar · View at Scopus
  85. W. E. Schutzer, J. F. Reed, and S. L. Mader, “Decline in caveolin-1 expression and scaffolding of G protein receptor kinase-2 with age in Fischer 344 aortic vascular smooth muscle,” The American Journal of Physiology, vol. 288, no. 5, pp. H2457–H2464, 2005. View at Publisher · View at Google Scholar · View at Scopus
  86. B. Razani and M. P. Lisanti, “Caveolin-deficient mice: insights into caveolar function and human diseases,” Journal of Clinical Investigation, vol. 108, no. 11, pp. 1553–1561, 2001. View at Publisher · View at Google Scholar · View at Scopus
  87. B. Razani and M. P. Lisanti, “Two distinct caveolin-1 domains mediate the functional interaction of caveolin-1 with protein kinase A,” The American Journal of Physiology, vol. 281, no. 4, pp. C1241–C1250, 2001. View at Google Scholar · View at Scopus
  88. M. Drab, P. Verkade, M. Elger et al., “Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice,” Science, vol. 293, no. 5539, pp. 2449–2452, 2001. View at Publisher · View at Google Scholar · View at Scopus
  89. R. Winstel, S. Freund, C. Krasel, E. Hoppe, and M. J. Lohse, “Protein kinase cross-talk: membrane targeting of the β-adrenergic receptor kinase by protein kinase C,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 5, pp. 2105–2109, 1996. View at Publisher · View at Google Scholar · View at Scopus
  90. T. T. Chuang, H. Le Vine, and A. De Blasi, “Phosphorylation and activation of β-adrenergic receptor kinase by protein kinase C,” Journal of Biological Chemistry, vol. 270, no. 31, pp. 18660–18665, 1995. View at Publisher · View at Google Scholar · View at Scopus
  91. M. Shih and C. C. Malbon, “Oligodeoxynucleotides antisense to mRNA encoding protein kinase A, protein kinase C, and β-adrenergic receptor kinase reveal distinctive cell-type- specific roles in agonist-induced desensitization,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 25, pp. 12193–12197, 1994. View at Publisher · View at Google Scholar · View at Scopus
  92. S. W. Kubalak and J. G. Webb, “Angiotensin II enhancement of hormone-stimulated cAMP formation in cultured vascular smooth muscle cells,” The American Journal of Physiology, vol. 264, no. 1, pp. H86–H96, 1993. View at Google Scholar · View at Scopus
  93. T. Nabika, Y. Nara, and Y. Yamori, “Angiotensin II and phorbol ester enhance isoproterenol- and vasoactive intestinal peptide (VIP)-induced cyclic AMP accumulation in vascular smooth muscle cells,” Biochemical and Biophysical Research Communications, vol. 131, no. 1, pp. 30–36, 1985. View at Google Scholar · View at Scopus
  94. T. Inoue, M. Zaichuan, D. G. Gillespie, R. K. Dubey, and E. K. Jackson, “Angiotensin receptor subtype 1 mediates angiotensin II enhancement of isoproterenol-induced cyclic AMP production in preglomerular microvascular smooth muscle cells,” Journal of Pharmacology and Experimental Therapeutics, vol. 288, no. 3, pp. 1229–1234, 1999. View at Google Scholar · View at Scopus
  95. R. Mokkapatti, S. J. Vyas, G. G. Romero et al., “Modulation by angiotensin II of isoproterenol-induced cAMP production in preglomerular microvascular smooth muscle cells from normotensive and genetically hypertensive rats,” Journal of Pharmacology and Experimental Therapeutics, vol. 287, no. 1, pp. 223–231, 1998. View at Google Scholar · View at Scopus
  96. A. Brizzolara-Gourdie and J. G. Webb, “Angiotensin II potentiates vasodilation of rat aorta by cAMP elevating agonists,” Journal of Pharmacology and Experimental Therapeutics, vol. 281, no. 1, pp. 354–359, 1997. View at Google Scholar · View at Scopus
  97. W. F. Jackson, “Ion channels and vascular tone,” Hypertension, vol. 35, no. 1, part 2, pp. 173–178, 2000. View at Google Scholar · View at Scopus
  98. K. Fujii, U. Onaka, K. Goto, A. Isao, and M. Fujishima, “Impaired isoproterenol-induced hyperpolarization in isolated mesenteric arteries of aged rats,” Hypertension, vol. 34, no. 2, pp. 222–228, 1999. View at Google Scholar · View at Scopus
  99. E. Thorin and N. Thorin-Trescases, “Vascular endothelial ageing, heartbeat after heartbeat,” Cardiovascular Research, vol. 84, no. 1, pp. 24–32, 2009. View at Publisher · View at Google Scholar · View at Scopus
  100. P. M. Vanhoutte, “Endothelial adrenoceptors,” Journal of Cardiovascular Pharmacology, vol. 38, no. 5, pp. 796–808, 2001. View at Google Scholar
  101. R. E. Howell, S. M. Albelda, M. L. Daise et al., “Characterization of beta-adrenergic receptors in cultured human and bovine endothelial cells,” Journal of Applied Physiology, vol. 65, no. 3, pp. 1251–1257, 1988. View at Google Scholar
  102. L. Brawley, A. M. Shaw, and A. MacDonald, “β1-, β2- and atypical β-adrenoceptor-mediated relaxation in rat isolated aorta,” The British Journal of Pharmacology, vol. 129, no. 4, pp. 637–644, 2000. View at Google Scholar · View at Scopus
  103. K. B. Kang, A. van der Zypp, and H. Majewski, “Endogenous nitric oxide attenuates beta-adrenoceptor-mediated relaxation in rat aorta,” Clinical and Experimental Pharmacology and Physiology, vol. 34, no. 1-2, pp. 95–101, 2007. View at Google Scholar
  104. A. van der Zypp, K. B. Kang, and H. Majewski, “Age-related involvement of the endothelium in β-adrenoceptor-mediated relaxation of rat aorta,” European Journal of Pharmacology, vol. 397, no. 1, pp. 129–138, 2000. View at Publisher · View at Google Scholar · View at Scopus
  105. T. A. Deisher, S. Mankani, and B. B. Hoffman, “Role of cyclic AMP-dependent protein kinase in the diminished beta-adrenergic responsiveness of vascular smooth muscle with increasing age,” Journal of Pharmacology and Experimental Therapeutics, vol. 249, no. 3, pp. 812–819, 1989. View at Google Scholar · View at Scopus
  106. M. Ishikawa, Y. Ouchi, M. Akishita et al., “Age-related decrease in the effect of parathyroid hormone-related protein on cytosolic free calcium level and tension in rat aortic smooth muscle,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 351, no. 5, pp. 517–522, 1995. View at Google Scholar · View at Scopus
  107. P. Penela, C. Murga, C. Ribas, V. Lafarga, and F. Mayor, “The complex G protein-coupled receptor kinase 2 (GRK2) interactome unveils new physiopathological targets,” The British Journal of Pharmacology, vol. 160, no. 4, pp. 821–832, 2010. View at Publisher · View at Google Scholar · View at Scopus
  108. N. Fraeyman, E. Van de Velde, A. Van Ermen et al., “Effect of maturation and aging on β-adrenergic signal transduction in rat kidney and liver,” Biochemical Pharmacology, vol. 60, no. 12, pp. 1787–1795, 2000. View at Publisher · View at Google Scholar · View at Scopus
  109. H. A. Rockman, W. J. Koch, and R. J. Lefkowitz, “Seven-transmembrane-spanning receptors and heart function,” Nature, vol. 415, no. 6868, pp. 206–212, 2002. View at Publisher · View at Google Scholar · View at Scopus
  110. J. M. Preuss, P. J. Rigby, and R. G. Goldie, “The influence of animal age on β-adrenoceptor density and function in tracheal airway smooth muscle,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 360, no. 2, pp. 171–178, 1999. View at Publisher · View at Google Scholar · View at Scopus
  111. M. Sastre, J. Guimon, and J. A. Garcia-Sevilla, “Relationships between beta- and alpha2-adrenoceptors and G coupling proteins in the human brain: effects of age and suicide,” Brain Research, vol. 892, no. 2, pp. 242–255, 2001. View at Google Scholar