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CHANGES IN ANGIOTENSIN II METABOLISM CONTRIBUTE TO THE INCREASED PRESSOR RESPONSE TO ANGIOTENSIN AFTER CHRONIC TREATMENT WITH l ‐NAME IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Author(s) -
Yang Y.,
Macdonald GJ,
Duggan KA
Publication year - 1996
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1996.tb02796.x
Subject(s) - angiotensin ii , endocrinology , medicine , blood pressure , renin–angiotensin system , nitric oxide synthase , mean arterial pressure , radioimmunoassay , metabolism , nitric oxide , chemistry , heart rate
SUMMARY 1. Administration of nitric oxide (NO) synthase inhibitors, such as l ‐NAME, is associated with an increase in blood pressure and an increase in pressor responsiveness to infused angiotensin II (AngII). The present study was designed to investigate the contribution of changes in the metabolism of AngII to the enhanced pressor response to AngII in the spontaneously hypertensive rat (SHR; 14 weeks old) chronically treated with l ‐NAME. 2. Group I rats received l ‐NAME for 7 days (5 mg/kg per day) in their drinking water. Group II rats received water only. On day 7, rats were anaesthetized and metabolic clearance studies were performed. AngII concentrations in plasma and infusate were measured by radioimmunoassay. 3. Urinary NO 2 was unchanged after l ‐NAME treatment, while NO 3 decreased compared with control. Mean arterial pressure (MAP) was higher in the l ‐NAME treated rats than in control. After 30min infusion of AngII, MAP increased significantly in both groups, although the increase was larger in l ‐NAME‐treated than control rats. The metabolic clearance rate of AngII was significantly lower in l ‐NAME‐treated rats than in the control group. 4. We conclude that chronic NO synthase inhibitors, such as l ‐NAME, cause a decrease in the rate at which AngII is metabolized. This decrease, in combination with the increase in the number of vascular AngII receptors, may account for the reported increase in pressor responsiveness to infused AngII.