Cardiovascular Autonomic Activity Modulation By Nitric Oxide Synthases Mediates The Augmented Enalapril‐Evoked Hypotension In Ethanol‐Fed Female Rats

Abstract

Chronic ethanol enhances the hypotensive action of enalapril in female rats. Here, we investigated whether cardiovascular auto‐nomic modulation by nitric oxide synthases (NOS) contributes to such enhancement. We investigated the effect of inhibition of eNOS [N5‐(1‐iminoethyl)‐L‐ornithine; L‐NIO], nNOS (Nω‐propyl‐L‐arginine; NPLA), or iNOS (1400W) on blood pressure (BP), myocardial contractility (dP/dtmax), and power spectral indices of hemodynamic variability in telemetered female rats fed with ethanol (5% w/v, 8 weeks) or control liquid diet in absence or presence of enalapril. In control rats, enalapril‐evoked hypotension was abolished by L‐NIO, but not by NPLA or 1400W, suggesting a preferential role for eNOS in this response. In ethanol‐fed, the greater enalapril hypotension was associated with reductions in (i) dP/dtmax, (ii) low‐frequency/high‐frequency ratio of interbeat intervals, suggesting cardiac parasympathetic dominance, and (iii) low‐frequency band of systolic BP, a marker of vasomotor sympathetic tone. While all NOS inhibitors attenuated the hemodynamic and autonomic responses of enalapril in ethanol‐fed rats, L‐NIO was the most efficacious in rectifying enalapril‐evoked autonomic responses. These findings implicate NOS isoforms, particularly eNOS, in autonomic imbalances that leads to the augmented enalapril hypotension in ethanol‐fed rats.