Modulatory Roles Of Constitutive and Inducible NOS In The Ethanol‐Evoked Hypotension And Cardiac Autonomic dysfunction In female rats

Abstract

We recently reported that chronic ethanol lowers blood pressure (BP) in female rats. This study investigated the roles of constitutive and inducible NOS in ethanol hypotension and associated changes in hemodynamic variability. Changes caused by inhibition of eNOS (L-NIO, 20 mg/kg), nNOS (NPLA, 1 mg/kg), or iNOS (1400W, 5 mg/kg) in BP, heart rate (HR), myocardial contractility (dP/dtmax), and power spectral indices of hemodynamic variability were evaluated in telemetered female rats receiving ethanol (5%, w/v, 8 weeks) or control liquid diet. Ethanol increased plasma nitrite/nitrate and aortic eNOS expression, and reduced BP, myocardial contractility (+dP/dtmax), low-frequency bands of interbeat intervals (IBILF, 0.25–0.75 Hz) and IBILF/HF ratio; high-frequency bands (IBIHF, 0.75–3 Hz) were increased by ethanol, suggesting parasympathetic overactivity. L-NIO caused greater increases in BP in control than ethanol-fed rats. IBILF/HF and +dP/dtmax were reduced by L-NIO to similar extents in the two rat groups. NPLA uncovered additional reductions in BP, +dP/dtmax, and IBILF/HF only in ethanol-fed rats. No hemodynamic modifications were caused by 1400W in either rat group. In summary, nNOS acts tonically to offset the detrimental cardiovascular actions of ethanol in female rats. Moreover, the enhanced NO bioavailability in ethanol-fed rats may explain the reduced pressor action of L-NIO.