Intrarenal Aminopeptidase N Inhibition Augments Natriuretic Responses to Angiotensin III in Angiotensin Type 1 Receptor–Blocked Rats

The renal angiotensin angiotensin type 2 receptor has been shown to mediate natriuresis, and angiotensin III, not angiotensin II, may be the preferential angiotensin type 2 receptor activator of this response. Angiotensin III is metabolized to angiotensin IV by aminopeptidase N. The present study hy...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2007-03, Vol.49 (3, Part 2 Suppl), p.625-630
Main Authors: Padia, Shetal H, Kemp, Brandon A, Howell, Nancy L, Siragy, Helmy M, Fournie-Zaluski, Marie-Claude, Roques, Bernard P, Carey, Robert M
Format: Article
Language:English
Subjects:
Angiotensin II Type 1 Receptor Blockers - administration & dosage
Angiotensin III - pharmacology
Animals
Arterial hypertension. Arterial hypotension
Benzimidazoles - administration & dosage
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
CD13 Antigens - antagonists & inhibitors
Clinical manifestations. Epidemiology. Investigative techniques. Etiology
Enzyme Inhibitors - pharmacology
Experimental diseases
Medical sciences
Methionine - analogs & derivatives
Methionine - pharmacology
Models, Animal
Natriuresis - drug effects
Natriuretic Agents - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Angiotensin - drug effects
Sodium - urine
Tetrazoles - administration & dosage
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Summary:The renal angiotensin angiotensin type 2 receptor has been shown to mediate natriuresis, and angiotensin III, not angiotensin II, may be the preferential angiotensin type 2 receptor activator of this response. Angiotensin III is metabolized to angiotensin IV by aminopeptidase N. The present study hypothesizes that inhibition of aminopeptidase N will augment natriuretic responses to intrarenal angiotensin III in angiotension type 1 receptor–blocked rats. Rats received systemic candesartan for 24 hours before the experiment. After a 1-hour control, cumulative renal interstitial infusion of angiotensin III at 3.5, 7, 14, and 28 nmol/kg per minute (each dose for 30 minutes) or angiotensin III combined with aminopeptidase N inhibitor PC-18 was administered into 1 kidney. The contralateral control kidney received renal interstitial infusion of vehicle. In kidneys infused with angiotensin III alone, renal sodium excretion rate increased from 0.05±0.01 μmol/min in stepwise fashion to 0.11±0.01 μmol/min at 28 nmol/kg per minute of angiotensin III (overall ANOVA F=3.68; P
ISSN:0194-911X
1524-4563
DOI:10.1161/01.HYP.0000254833.85106.4d