title: In vivo occupancy of angiotensin II subtype 1 receptors in rat renal medullary interstitial cells.
abstract: 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 administration. In anesthetized rats, we investigated if reduced vascular delivery due to angiotensin II-induced renal vasoconstriction or, alternatively, prior occupancy of these sites by endogenous angiotensins modulates angiotensin II subtype 1 receptor binding to renal medullary interstitial cells in vivo using electron microscopic autoradiography. Using 125I-angiotensin II, administered systemically, as a radioligand, binding in control rats occurred predominantly in the glomeruli and proximal tubules, while only low binding was observed in the inner stripe of the outer medulla. Pretreatment of rats with unlabeled [Sar1,Ile8]angiotensin II or with the angiotensin II subtype 1 receptor antagonist losartan before receiving the radioligand completely abolished binding to all sites. Renal vasodilatation induced by sodium nitroprusside or use of the radiolabeled antagonist analogue 125I-[Sar1,Ile8]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 cortical sites but also to the sites in the inner stripe of the outer medulla. Electron microscopic autoradiographs of the inner stripe detected binding in the interstitial cells only in rats treated with chronic salt loading or perindopril. These results suggest that endogenous angiotensins may modulate binding of circulating angiotensin II to the interstitial cells in vivo, and these angiotensin II receptor-bearing cells are more likely to be more responsive to interstitial angiotensin II than to the circulating hormone.
authors.affiliation: Department of Medicine, University of Melbourne, Austin Hospital, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Zhuo
authors.forename: D
authors.initials: D
authors.lastname: Alcorn
authors.forename: J
authors.initials: J
authors.lastname: McCausland
authors.forename: D
authors.initials: D
authors.lastname: Casley
authors.forename: F A
authors.initials: FA
authors.lastname: Mendelsohn
mesh_terms: D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000378:metabolism; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D001713:Biphenyl Compounds / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D019808:Losartan; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D019808:Losartan