Mapping of angiotensin II receptor subtypes in peripheral tissues of spontaneously hypertensive rats by in vitro autoradiography.
1. The regulation of angiotensin II (AII) receptor subtypes was studied in peripheral tissues of 20 week old male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats. 2. AII receptor binding was determined by a quantitative in vitro autoradiography using [125I]-[Sar1,Ile8]AII as a ligand on the kidney, adrenal gland, thoracic aorta and heart. CV-11974, a specific AT1 receptor antagonist, and CGP42112B, a specific AT2 antagonist, were used in competition with [125I]-[Sar1,Ile8]AII to differentiate AT1 and AT2 receptor binding. 3. The relative abundance of each subtype was very similar between SHR and WKY rats. In both strains of rats, the adrenal cortex contained predominantly AT1 receptors, while AT2 receptors predominated in the adrenal medulla. The kidney contained exclusively AT1 receptors over glomeruli, proximal tubules and outer medulla. AT1 receptors were predominant in the thoracic aorta and heart. 4. As for relative receptor density, important differences were observed between SHR and WKY rats. In SHR, the adrenal cortex, outer medulla of the kidney, and heart displayed higher AT1 receptor density than WKY rats. 5. These results indicate that the expression of AT1 receptors is differently regulated in some important targets of AII in SHR, and suggest that the altered regulation of AT1 receptor presented in this study should be relevant to the pathophysiological features of SHR.
Song
K
K
Department of Pharmacology, Osaka Medical College, Japan.
Kurobe
Y
Y
Kanehara
H
H
Wada
T
T
Inada
Y
Y
Nishikawa
K
K
Miyazaki
M
M
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000235:genetics*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D009842:Oligopeptides; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C060894:CGP 42112A; D000803:Angiotensin I; C081643:candesartan