RENAL ANGIOTENSIN-II RECEPTOR REGULATION IN 2-KIDNEY, ONE-CLIP HYPERTENSIVE RATS - EFFECT OF ACE-INHIBITION

Local renal and plasma renin-angiotensin systems (RAS) both play an im portant role in blood pressure regulation during the development of tw o-kidney, one clip Goldblatt hypertension (2K1C) through their vasoact ive component, angiotensin II (Ang II). Our goal was to characterize g lomerular and preglomerular vascular Ang II receptors during the diffe rent stages of development of hypertension in 2K1C rats (2-, 4-, 8-, a nd 16-weeks postoperative) using Ang II antagonists [Sar(1),Ile(8)]-An g II, losartan, and PD 123319 and their regulation after angiotensin-c onverting enzyme (ACE) inhibition by captopril. Competitive binding st udies showed that the only Ang II receptor detected on both glomeruli and preglomerular vessels of all groups (2-, 4-, 8-, and 16-week 2K1C rats, control rats, and captopril-treated rats) was the Ang II type 1 receptor (AT(1)). Vascular AT(1) receptor density (B-max) was signific antly lower in only the 16-week 2K1C group, whereas glomerular B-max w as significantly lower in 2K1C rats at 2-, 4-, and 8-weeks. Vascular a nd glomerular receptor densities were both significantly higher in cap topril-treated rats than in nontreated rats. We therefore conclude tha t in 2K1C rats, Ang II receptors on preglomerular vessels and glomerul i are regulated differentially during the development of hypertension and after ACE inhibition. Our results suggest that glomerular Ang II r eceptors are regulated by systemic plasma Ang II levels, whereas vascu lar Ang II receptors are not. However, when renal and systemic RASs ar e both blocked, these receptors are upregulated but are no longer diff erentially regulated.