A COMPARISON OF THE ACTIONS OF CILAZAPRIL IN NORMAL, DIETARY SODIUM-DEPLETED AND 2-KIDNEY, ONE CLIP GOLDBLATT HYPERTENSIVE ANESTHETIZED RATS

Objective: This study aimed to examine the role of the renin-angiotensin system in the regulation of kidney haemodynamic and excretory function when angiotensin II levels were modestly and markedly raised. Design: Three groups of male Sprague-Dawley rats were used: control rats fed a sodium-replete diet; rats fed a sodium-deficient diet for 2 weeks; and two-kidney, one clip (2K1C) Goldblatt hypertensive rats, 4-5 weeks postclipping. Methods: The rats were acutely anaesthetized with sodium pentobarbitone and prepared for renal function measurements. The converting enzyme inhibitor, cilazapril, was then infused at increasing dose levels to progressively block the renin-angiotensin system. Results: Cilazapril did not affect blood pressure in sodium-replete animals; it raised RBF and increased water and sodium excretion. In dietary sodium-depleted rats, cilazapril decreased blood pressure and increased RBF, water and sodium excretion at the lower doses of the drug; however, at vasodepressor doses, water and sodium excretion fell towards baseline values. In 2K1C Goldblatt hypertensive rats, cilazapril maximally decreased blood pressure whilst the non-clipped kidney blood flow, filtration rate and fluid excretion rates were similar to dietary sodium-depleted rats; in contrast, the clipped kidney filtration rate was well maintained and fluid excretion was raised in a dose-related fashion. Conclusion: These results show that during gradual cilazapril administration, renal function is well preserved in 2K1C Goldblatt hypertensive rats when pressure is progressively reduced.