Effects of Angiotensin Receptor Subtype Inhibitors on Plasma Angiotensin Clearance

The aim of this study was to determine whether angiotensin receptor subtypes play a role in angiotensin clearance from plasma. Angiotensin metabolic clearance rate was measured in rats by the constant infusion method. Increasing doses of angiotensin II were infused for 15 minutes, and blood was samp...

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Bibliographic Details
Published in:	Hypertension (Dallas, Tex. 1979) Vol. 23; no. 6, Part 2; pp. 853 - 856
Main Authors:	Veniace, Melchiore A, Mento, Peter F, Maita, Mary E, Wilkes, Barry M
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Heart Association, Inc 01-06-1994 Hagerstown, MD Lippincott
Subjects:	Angiotensin II - blood Angiotensin Receptor Antagonists Animals Biological and medical sciences Biphenyl Compounds - pharmacology Cell receptors Cell structures and functions Fundamental and applied biological sciences. Psychology Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors Imidazoles - pharmacology Losartan Male Metabolic Clearance Rate - drug effects Molecular and cellular biology Pyridines - pharmacology Rats Rats, Sprague-Dawley Tetrazoles - pharmacology Renin angiotensin system Vertebrata Mammalia Rat Animal Peptide hormone Rodentia Exploration Clearance Angiotensin II Blood plasma Hormonal receptor
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Summary:	The aim of this study was to determine whether angiotensin receptor subtypes play a role in angiotensin clearance from plasma. Angiotensin metabolic clearance rate was measured in rats by the constant infusion method. Increasing doses of angiotensin II were infused for 15 minutes, and blood was sampled for angiotensin II. The type 1 angiotensin II receptor antagonist losartan decreased the apparent metabolic clearance rate by >50% at low-dose infusion, suggesting that type 1 angiotensin II receptors are involved in angiotensin II clearance from plasma. At higher angiotensin infusion rates, the metabolic clearance rate of angiotensin was unaffected. To dissect the contribution of renin-generated angiotensin, additional experiments were performed in nephrectomized rats. In anephric rats, angiotensin clearance was unaffected by type 1 angiotensin II receptor inhibition. In contrast, the type 2 angiotensin II receptor ligand PD123319 in intact rats caused a >50% increase in metabolic clearance rate of angiotensin at higher infusion rates (P<.05). In anephric rats, the type 2 angiotensin II receptor ligand alone or combined with type 1 receptor inhibition was without effect on the metabolic clearance rate or the T1/2 for angiotensin disappearance. These data argue against a role for type 1 or 2 angiotensin II receptors as clearance receptors. Increased clearance of angiotensin by type 2 receptor blockade in the presence but not the absence of kidneys suggests an alternative renal mechanism by which selective type 2 ligands may alter angiotensin effects.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0194-911X 1524-4563
DOI:	10.1161/01.HYP.23.6.853