Cardiovascular autonomic modulation by nitric oxide synthases accounts for the augmented enalapril-evoked hypotension in ethanol-fed female rats.

Abstract

In this study, we investigated the role of nitric oxide synthase (NOS) isoforms in the enhanced enalapril-evoked hypotension in ethanol-fed female rats by examining the effect of the selective inhibitors of eNOS [N(5)-(1-iminoethyl)-l-ornithine; l-NIO], nNOS (N(ω)-propyl-l-arginine; NPLA), or iNOS (1400W) inhibition on the cardiovascular effects of enalapril in ethanol- (5% w/v) fed rats and in their pair-fed controls. In liquid diet-fed control rats, enalapril- (10 mg/kg) evoked hypotension was abolished by l-NIO (20 mg/kg), but not by NPLA (1 mg/kg) or 1400W (5 mg/kg), suggesting a preferential role for eNOS in this response. Enalapril had no effect on spectral indices of hemodynamic variability or +dP/dtmax (myocardial contractility). However, in ethanol-fed rats, the greater enalapril-evoked hypotension was associated with reductions in (i) +dP/dtmax, (ii) low-frequency/high-frequency ratio of interbeat intervals (IBILF/HF), suggesting cardiac parasympathetic dominance, and (iii) low-frequency spectral band of systolic blood pressure (BP), a marker of vasomotor sympathetic tone. While NPLA or 1400W attenuated the enalapril-evoked hemodynamic and autonomic responses in ethanol-fed rats, l-NIO virtually abolished the hypotensive response and was more efficacious in rectifying autonomic responses to enalapril. Together, these findings implicate NOS isoforms, particularly eNOS, in the altered cardiovascular autonomic control that leads to the augmented enalapril-evoked hypotension in ethanol-fed female rats.

• Authors: Mahmoud M El-Mas, Abdel A Abdel-Rahman
• Journal: Alcohol (Fayetteville, N.Y.) (Alcohol) Vol. 47 Issue 4 Pg. 339-46 (Jun 2013) ISSN: 1873-6823 [Electronic] United States
• PMID: 23683529 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Ethanol
• Enalapril
• Nitric Oxide Synthase Type I
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Nos1 protein, rat
• Nos2 protein, rat
• Nos3 protein, rat

Topics

• Alcohol Drinking (adverse effects, metabolism, physiopathology)
• Animals
• Arterial Pressure (drug effects)
• Autonomic Nervous System (drug effects, physiopathology)
• Cardiovascular System (innervation)
• Disease Models, Animal
• Enalapril
• Enzyme Inhibitors (pharmacology)
• Ethanol (toxicity)
• Female
• Heart Rate (drug effects)
• Hypotension (chemically induced, enzymology, physiopathology)
• Nitric Oxide Synthase Type I (antagonists & inhibitors, metabolism)
• Nitric Oxide Synthase Type II (antagonists & inhibitors, metabolism)
• Nitric Oxide Synthase Type III (antagonists & inhibitors, metabolism)
• Rats
• Rats, Sprague-Dawley
• Time Factors