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Advances in Pharmacological Sciences
Volume 2013 (2013), Article ID 718313, 8 pages
http://dx.doi.org/10.1155/2013/718313
Research Article

Comparative In Vitro Effects of Calcineurin Inhibitors on Functional Vascular Relaxations of Both Rat Thoracic and Abdominal Aorta

1Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5
2Department of Medicine, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada S7J 5B6
3Saskatchewan Transplant Program, Royal University Hospital, 103 Hospital Drive, Saskatoon, SK, Canada S7N 0W8

Received 17 April 2013; Accepted 2 June 2013

Academic Editor: Masahiro Oike

Copyright © 2013 Ashok Jadhav et al. 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.

Abstract

Background and Aim. Calcineurin inhibitors (CNIs) have shown to develop hypertension in transplant patients. The in vitro incubation effects of cyclosporine (CsA) and tacrolimus (Tac) on vascular relaxations of rat thoracic aorta (TA) and abdominal aorta (AA) need to be investigated. Methods. The optimal concentrations of CsA (1.0 mg/mL) and Tac (0.1 mg/mL) used to compare endothelium-dependent (acetylcholine (ACh)) and endothelium-independent (sodium nitroprusside (SNP)) vascular relaxation against the agonists in phenylephrine (PE-) constricted TA and AA of 13-week-old male Sprague Dawley rats ( ). Results. In TA, the maximal vasodilator response elicited by ACh (control: 98%) was significantly ( ) inhibited by CsA ( 10%) but not by Tac ( 97%). In AA, (control: IC50 50 nM; 100%) CsA (IC50 7 μM; ( ) showed strong sensitivity to inhibit ACh-dependent vascular relaxation than Tac (IC50 215 nM ( ); 98%). CsA and Tac failed to affect the inhibitory responses to SNP in both TA and AA. Conclusion. CsA exerts profound inhibitory effect on endothelium-dependent vasodilatation as compared to Tac in both TA and AA. Aortic rings from the thoracic region are more sensitive to CNIs, since the vasodilator response to ACh is solely mediated by NO while in the AA, ACh likely recruits other endothelial mediators besides NO to maintain vasodilatation.