IN-VIVO OCCUPANCY OF ANGIOTENSIN-II SUBTYPE-1 RECEPTORS IN RAT RENAL-CELLS

Angiotensin II receptor binding sites in type 1 interstitial cells in the inner stripe of the outer medulla are readily labeled in vitro by the radioligand but not in vivo after systemic radioligand administrat ion. In anesthetized rats, we investigated if reduced vascular deliver y due to angiotensin II-induced renal vasoconstriction or, alternative ly, prior occupancy of these sites by endogenous angiotensins modulate s angiotensin II subtype 1 receptor binding to renal medullary interst itial cells in vivo using electron microscopic autoradiography. Using I-125-angiotensin II, administered systemically, as a radioligand, bin ding in control rats occurred predominantly in the glomeruli and proxi mal tubules, while only low binding was observed in the inner stripe o f the outer medulla. Pretreatment of rats with unlabeled [Sar(1),Ile(8 )]angiotensin II or with the angiotensin II subtype 1 receptor antagon ist losartan before receiving the radioligand completely abolished bin ding to all sites. Renal vasodilatation induced by sodium nitroprussid e or use of the radiolabeled antagonist analogue I-125-[ Sar(1),Ile(8) ]angiotensin II did not alter binding to the inner stripe. In contrast , chronic salt loading or inhibition of angiotensin-converting enzyme by perindopril significantly increased binding not only to the cortica l sites but also to the sites in the inner stripe of the outer medulla . Electron microscopic autoradiographs of the inner stripe detected bi nding in the interstitial cells only in rats treated with chronic salt loading or perindopril. These results suggest that endogenous angiote nsins may modulate binding of circulating angiotensin II to the inters titial cells in vivo, and these angiotensin II receptor-bearing cells are more likely to be more responsive to interstitial angiotensin II t han to the circulating hormone.