Document Detail

Improved survival in rats administered NG-nitro L-arginine methyl ester due to converting enzyme inhibition.
MedLine Citation:
PMID:  8797148     Owner:  NLM     Status:  MEDLINE    
Blockade of the renin-angiotensin system (RAS) prevents the increase in blood pressure (BP) induced by chronic administration of NG-nitro L-arginine methyl ester (L-NAME) in rats. In the present study, we showed how a converting enzyme inhibitor can prevent the end-stage tissue damage due to chronic nitric oxide (NO) synthase blockade and thus improve the survival rate. Three experiments were performed. In the first, rats (n = 10) were given L-NAME (50 mg/kg) and 10 other rats were given L-NAME plus quinapril (10 mg/kg) starting 1 month after L-NAME administration. Ten untreated rats were used as controls. Rats were killed after 2 months, and the RAS, renal function, and renal morphology were analyzed. In the second experiment, a similar protocol was used, and function and morphological damage in renal slices and cervical medullary tissue were assessed after 4 months of L-NAME and 3 months of quinapril + L-NAME. In the third experiment, a similar protocol was used, but to establish survival curves, the animals were not killed. L-NAME significantly increased BP without causing any significnat changes in plasma renin activity (PRA) at 2 months. The aortic wall cyclic GMP content was significantly decreased, and the angiotensin-converting enzyme (ACE) activity was increased by L-NAME. Quinapril significantly reversed the high BP induced by L-NAME without changing the decrease in the aortic wall cyclic GMP. Two-month L-NAME treatment decreased renal function and damaged renal tissue. Quinapril prevented both proteinuria and morphological damage. Four-month L-NAME treatment induced renal end-stage damage and infarctions of the cervical medulla. Quinapril prevented this end-stage damage in the kidney and cervical medulla. Quinapril therefore prevented the increased mortality due to L-NAME. Hence, inhibition of ACE, despite its lack of effect on arterial wall cyclic GMP, does reverse the hypertension and prevent end-stage vascular damage induced by chronic L-NAME in target organs.
J B Michel; Y Xu; S Blot; M Philippe; G Chatellier
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  28     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1997-01-06     Completed Date:  1997-01-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  142-8     Citation Subset:  IM    
INSERM U367, Paris, France.
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MeSH Terms
Angiotensin-Converting Enzyme Inhibitors / pharmacology*,  therapeutic use
Aorta / metabolism
Blood Pressure / drug effects
Enzyme Inhibitors / toxicity*
Isoquinolines / pharmacology*,  therapeutic use
Kidney / drug effects*,  pathology
Kidney Diseases / chemically induced,  prevention & control*
Kidney Function Tests
NG-Nitroarginine Methyl Ester / antagonists & inhibitors,  toxicity*
Nitric Oxide Synthase / antagonists & inhibitors*
Rats, Wistar
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Enzyme Inhibitors; 0/Isoquinolines; 0/Tetrahydroisoquinolines; 50903-99-6/NG-Nitroarginine Methyl Ester; 82586-55-8/quinapril; EC Oxide Synthase

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