Exacerbation of myocardial dysfunction and autonomic imbalance contributes to the estrogen-dependent chronic hypotensive effect of ethanol in female rats.
Our previous studies showed that the hypotensive effect of chronic ethanol in female rats is reduced by ovariectomy (OVX) rats and was restored after estrogen replacement (OVXE(2)). Further, in randomly cycling rats, chronic ethanol increased cardiac parasympathetic dominance and subsequently reduced myocardial contractility and blood pressure (BP). In this study, we tested the hypothesis that alterations in myocardial contractility and sympathovagal control account for the E(2) exacerbation of the hemodynamic effects of ethanol. BP, myocardial contractility (+dP/dt(max)), and spectral cardiovascular autonomic profiles were evaluated in radiotelemetered OVX, and OVXE(2) rats receiving liquid diet with or without ethanol (5%, w/v) for 13 weeks. In OVX rats, ethanol caused modest hypotension along with significant increases in +dP/dt(max) during weeks 2-5. The high-frequency (IBI(HF), 0.75-3 Hz) and low-frequency (IBI(LF), 0.25-0.75 Hz) bands of interbeat intervals were briefly increased and decreased, respectively, by ethanol. Compared with its effects in OVX rats, chronic treatment of OVXE(2) rats with ethanol elicited significantly greater and more sustained reductions in systolic (SBP) and diastolic (DBP) blood pressures and +dP/dt(max). Altered sympathovagal balance and parasympathetic overactivity were more evident in ethanol-treated OVXE(2) rats as suggested by the sustained: (i) increases in high-frequency bands of interbeat intervals (IBI(HF), 0.75-3 Hz), and (ii) decreases in low-frequency IBI bands (IBI(LF), 0.25-0.75 Hz), IBI(LF/HF) ratio and +dP/dt(max). The plasma ethanol concentration was not affected by changes in the hormonal milieu. These findings suggest that estrogen exacerbates the ethanol-evoked reductions in myocardial contractility and BP and the associated parasympathetic overactivity in female rats.
Department of Pharmacology and Toxicology, School of Medicine, East Carolina University, Greenville, NC 27834, USA. mahelm@hotmail.com
Mahmoud M
MM
el-Mas
Abdel A
AA
Abdel-Rahman
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D015914:Estrogen Replacement Therapy / Q000379:methods; D004967:Estrogens / Q000494:pharmacology* / Q000502:physiology*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
D004967:Estrogens; D000431:Ethanol