Ethanol lowers blood pressure in conscious female rats via enhancing the phosphorylation of myocardial neuronal nitric oxide synthase

Abstract

Intragastric (i.g.) ethanol lowers blood pressure (BP) in female rats via a reduction in cardiac output (CO) and stroke volume (SV). We tested the hypothesis that enhancement of myocardial nNOS and/or eNOS activity constitutes a cellular mechanism for ethanol‐evoked reductions in CO and BP. We investigated the effect of inhibition of nNOS (Nω‐propyl‐L‐arginine, NPLA) or eNOS [N5‐(1‐iminoethyl)‐L‐ornithine, L‐NIO] on hemodynamic, biochemical (nitrate/nitrite levels, NOx), and myocardial nNOS/eNOS phosphorylation elicited by ethanol (1 g/kg i.g.) in proestrus female rats. In saline‐pretreated rats, the hemodynamic effects of ethanol (reductions in BP, CO, and SV) were coupled with increases in plasma NOx and myocardial p‐nNOS, but not p‐eNOS, expression. nNOS inhibition by NPLA attenuated the hemodynamic effects of ethanol and associated increases in plasma NOx and cardiac p‐nNOS. eNOS inhibition by L‐NIO attenuated ethanol hypotension, but not concomitant CO/SV reductions. L‐NIO uncovered a dramatic increase in total peripheral resistance (TPR) in response to ethanol, which appeared to have offset the reduction in CO. These findings highlight: (i) myocardial nNOS as the cellular mechanism that underlies, in part, reductions in BP and CO caused by ethanol in female rats, and (ii) vascular eNOS‐NO signaling counterbalances ethanol‐induced increases in TPR.Supported by Grant R01 AA014441 from NIAAA.