Renal angiotensin II receptor regulation in two-kidney, one clip hypertensive rats: effect of ACE inhibition.
Local renal and plasma renin-angiotensin systems (RAS) both play an important role in blood pressure regulation during the development of two-kidney, one clip Goldblatt hypertension (2K1C) through their vasoactive component, angiotensin II (Ang II). Our goal was to characterize glomerular and preglomerular vascular Ang II receptors during the different stages of development of hypertension in 2K1C rats (2-, 4-, 8-, and 16-weeks postoperative) using Ang II antagonists [Sar1,Ile8]-Ang II, losartan, and PD 123319 and their regulation after angiotensin-converting enzyme (ACE) inhibition by captopril. Competitive binding studies 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 (AT1). Vascular AT1 receptor density (Bmax) was significantly lower in only the 16-week 2K1C group, whereas glomerular Bmax was significantly lower in 2K1C rats at 2-, 4-, and 8-weeks. Vascular and glomerular receptor densities were both significantly higher in captopril-treated rats than in nontreated rats. We therefore conclude that in 2K1C rats, Ang II receptors on preglomerular vessels and glomeruli are regulated differentially during the development of hypertension and after ACE inhibition. Our results suggest that glomerular Ang II receptors are regulated by systemic plasma Ang II levels, whereas vascular Ang II receptors are not. However, when renal and systemic RASs are both blocked, these receptors are upregulated but are no longer differentially regulated.
Amiri
F
F
Laboratory of Experimental Hypertension and Vasoactive Peptides, Clinical Research Institute of Montreal, Quebec, Canada.
Garcia
R
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology*; D006978:Hypertension, Renovascular / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000098:blood supply; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D002216:Captopril