Improved survival in rats administered NG-nitro L-arginine methyl ester due to converting enzyme inhibition.

Abstract

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.

• Authors: J B Michel, Y Xu, S Blot, M Philippe, G Chatellier
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 28 Issue 1 Pg. 142-8 (Jul 1996) ISSN: 0160-2446 [Print] United States
• PMID: 8797148 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Enzyme Inhibitors
• Isoquinolines
• Tetrahydroisoquinolines
• Nitric Oxide Synthase
• Quinapril
• NG-Nitroarginine Methyl Ester

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
• Animals
• 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
• Male
• NG-Nitroarginine Methyl Ester (antagonists & inhibitors, toxicity)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Quinapril
• Rats
• Rats, Wistar
• Tetrahydroisoquinolines