Enalapril and valsartan improve cyclosporine A-induced vascular dysfunction in spontaneously hypertensive rats

Cyclosporine A causes hypertension and nephrotoxicity in spontaneously hype rtensive rats (SHR). In the present study, arterial function was investigat ed using in vitro vascular preparations after long-term treatment with cycl osporine A. SHR received cyclosporine A (5 mg kg(-1) day(-1) s.c.) and high -Na+ diet for 6 weeks during the developmental phase of hypertension. Part of the rats were treated concomitantly either with the angiotensin converti ng enzyme inhibitor enalapril (30 mg kg(-1) day(-1) p.o.) or with an angiot ensin AT(1) receptor antagonist valsartan (3 or 30 mg kg(-1) day(-1) p.o.). In renal arteries, contractile responses to noradrenaline and angiotensin II, as well as relaxation responses to acetylcholine (endothelium-dependent ) and to sodium nitroprusside (endothelium-independent), were severely impa ired by cyclosporine A-treatment. There was also a trend for the dysfunctio n of the mesenteric arteries, but the impairment did not reach statistical difference. Enalapril and valsartan improved the impaired renal arterial fu nctions. Cyclosporine A-induced hypertension and nephrotoxicity seem to be associated with renal arterial dysfunction in SHR on high-Nai diet. Antagon ism of the renin-angiotensin system protects from vascular toxicity of cycl osporine A. (C) 2000 Elsevier Science B.V. All rights reserved.