%0 Journal Article
%T Comparative In Vitro Effects of Calcineurin Inhibitors on Functional Vascular Relaxations of Both Rat Thoracic and Abdominal Aorta
%A Ashok Jadhav
%A Venkat Gopalakrishnan
%A Ahmed Shoker
%J Advances in Pharmacological Sciences
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/718313
%X 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£¿¦ÌM; ( ) 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. 1. Introduction The post-transplantation vasculopathy is an important complication after organ transplantation [1]. The initial pathological event is thought to be an allograft endothelial dysfunction, a condition in which there is decreased generation of endothelium-derived relaxing factor, nitric oxide (NO). Either its synthesis is reduced or its increased quenching by oxidative stress is thought to result in increased vascular smooth muscle (VSM) tone and elevation in blood pressure that is accompanied by endothelial damage and loss of homeostatic regulatory property of the vascular wall [2]. Diminished NO function is thought to play a major role in the progression of post-transplantation vasculopathy [3]. Transplantation immunosuppressants such as calcineurin inhibitors (CNIs) have substantial effects on vascular reactivity, especially on NO synthesis [3]. The main two CNI drugs namely, cyclosporine A (CsA) and tacrolimus (Tac), have been suggested to impair vascular endothelial function via decreased generation of NO release along with increased generation vasoconstrictor peptide, endothelin-1 (ET-1) that leads to elevated vascular tone and resultant hypertension [4¨C8]. It is now well accepted that these effects of
%U http://www.hindawi.com/journals/aps/2013/718313/