Abstract
Cyclosporine A causes hypertension and nephrotoxicity in spontaneously hypertensive rats (SHR). In the present study, arterial function was investigated using in vitro vascular preparations after long-term treatment with cyclosporine 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 converting enzyme inhibitor enalapril (30 mg kg −1 day −1 p.o.) or with an angiotensin 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 impaired by cyclosporine A-treatment. There was also a trend for the dysfunction of the mesenteric arteries, but the impairment did not reach statistical difference. Enalapril and valsartan improved the impaired renal arterial functions. Cyclosporine A-induced hypertension and nephrotoxicity seem to be associated with renal arterial dysfunction in SHR on high-Na + diet. Antagonism of the renin–angiotensin system protects from vascular toxicity of cyclosporine A.
Published Version
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