Cardiovascular Effects Of Ethanol Research Articles

Abstract P609: Estrogen Receptor ERα Plays a Major Role in Oxidative Stress Dependent Myocardial Dysfunction Caused by Ethanol in Conscious Female Rats

Ethanol elicits estrogen (E 2 )-dependent myocardial oxidative stress and dysfunction in female rats. The aim of this study was to elucidate the role of the individual E 2 receptor (ER), ERα, ERβ, and the G protein-coupled estrogen receptor-1 (GPER), in the ethanol-evoked myocardial dysfunction. To achieve this goal, female rats in proestrus phase (highest E 2 level) received selective antagonist (200 μg/kg; i.v) of ERα (MPP), ERβ (PHTPP) or GPER (G15) or saline 30 min before ethanol (1 g/kg; i.v) or saline infusion. ERα blockade virtually abrogated ethanol-evoked myocardial dysfunction and hypotension, while ERβ blockade had no effect on the hypotensive response, but caused delayed attenuation of the ethanol-evoked reductions in left ventricular developed pressure and the rate of left ventricle pressure rise. GPER blockade caused delayed attenuation of both cardiovascular effects of ethanol. While all 3 ERs subtype antagonists attenuated the ethanol-evoked increases in myocardial catalase and ALDH2 activities, ERα blockade also inhibited myocardial catalase activity in the absence of ethanol. Ethanol-evoked elevation in myocardial ROS and enhancement of myocardial Akt, ERK1/2, eNOS and nNOS phosphorylation were attenuated by the 3 ER subtype antagonists. In conclusion, the findings support a greater role for ERα signaling in the E 2 -dependent myocardial oxidative stress and dysfunction caused by ethanol in proestrus rats.

Ethanol Attenuation of Peripheral NMDAR‐mediated Pressor Response

With clear dependence of ethanol actions on central NMDAR signaling, studies on the unexplored interaction between ethanol and peripheral cardiovascular NMDAR are warranted. We tested the hypothesis that peripheral vascular effects of ethanol might involve blockade of peripheral NMDAR; activation of the latter causes increases in blood pressure (BP), vascular ROS and NOS‐derived NO generation. Hemodynamic studies were conducted in seven groups (n=5–6) of conscious Sprague Dawley male rats that received: 1) Saline, 2) NMDA (125–1000 μg/kg), 3) Ethanol (1g/kg), 4) Ethanol + NMDA, 5) Saline infusion, 6) NMDA (180 μg/kg/min for 30 min) or 7) Ethanol + NMDA infusion. Ethanol or its vehicle (water) was administered by gavage 30 min prior to either bolus i.v. injections or infusion of NMDA or its vehicle. Ethanol, which had no effect on BP, caused a downward shift in the NMDA dose‐pressor response curve. It was important to evaluate the interaction between ethanol and sustained peripheral NMDAR activation (groups 5–7) because bolus NMDA elicited short lived (approx.1 min) response. Ethanol attenuated the sustained NMDA pressor response during the entire 30 min of NMDA infusion. Further, ethanol abrogated the peripheral NMDAR‐mediated increases in vascular NO and ROS generation. These findings provide new insight into a potential role for peripheral NMDAR in the cardiovascular effects of ethanol [NIH grant AA07839].

Cardiovascular Effects of Ethanol in Rats Selectively Bred for High or Low Sensitivity to the Hypnotic Effects of Ethanol

Cardiovascular Effects of Ethanol in Rats Selectively Bred for High or Low Sensitivity to the Hypnotic Effects of Ethanol

Cardiovascular Effects of Ethanol in Rats Selectively Bred for High or Low Sensitivity to the Hypnotic Effects of Ethanol

The cardiovascular effects of acute ethanol administration were studied in rats selectively bred for high (HAS) or low sensitivity (LAS) to the acute hypnotic effect of ethanol. In chronically cannulated, conscious animals, the intravenous administration of 1 g/kg of ethanol caused moderate hypotension and tachycardia in both HAS and LAS rats. The phenylephrine-induced reflex bradycardia and the baroreflex slope were significantly reduced by ethanol only in HAS and not in LAS rats. In urethane-anesthetized HAS rats, the baroreflex inhibitory action of ethanol was present under control conditions, but it was absent after depletion of endogenous GABA by treatment of the rats with 100 mg/kg of 3-mercaptopropionate. These findings confirm the role of endogenous GABA in the baroreflex inhibitory action of ethanol, and are compatible with the documented differential sensitivity of the GABAA, receptor complex to ethanol in HAS and LAS rats.

Cardiovascular effects of ethanol in anaesthetized, conscious and pithed rats

The influence of ethanol (2.0 g/kg p.o.) on heart rate and blood pressure in anaesthetized, conscious and pithed rats was studied. In anaesthetized rats we observed an increase in heart rate and a marked and very sudden decrease in blood pressure. In pithed rats blood pressure decreased more slowly than in anaesthetized and conscious animals and there were no changes in heart rate. These results show that the central nervous system may be responsible for the increase in heart rate and early phase of hypotension caused by acute ethanol administration. The slower decrease (up to 1 h) in blood pressure may be caused by central and different indirect peripheral mechanisms.

Maternal and fetal ethanol pharmacokinetics and cardiovascular responses in near-term pregnant sheep.

The disposition and cardiovascular effects of ethanol were studied in near-term pregnant sheep and their fetuses after intravenous infusions either to the mother or the fetus. Placental transfer of ethanol from mother to fetus was rapid, but transfer from the fetal to maternal circulation was impaired when ethanol was administered directly to the fetus. Plasma clearance of ethanol was similar from the mother and fetus in utero. In the maternal infusion experiments, both maternal and fetal heart rate increased with plasma ethanol concentration. However, in the fetal infusion experiments, both maternal and fetal heart rate increased with plasma ethanol concentration. However, in the fetal infusion experiments, fetal heart rate was inversely related to plasma ethanol concentrations while maternal mean arterial blood pressure increased with maternal plasma ethanol concentration. Further studies in neonatal lambs are needed to determine if ethanol has adverse effects on hemodynamics when the neonate is separated from its protective intrauterine environment.

Acute effects of ethanol and acetaldehyde on blood pressure and heart rate in disulfiram-treated and control rats.

The cardiovascular effects of ethanol and acetaldehyde were studied in control rats and rats pretreated with disulfiram. Ethanol administration to control rats decreased mean blood pressure and increased heart rate significantly. Injection of ethanol to disulfiram-treated rats decreased mean blood pressure, increases pulse pressure and increased heart rate and respiratory rate. The blood acetaldehyde levels were 10-15 times higher than those found in controls. The effects evoked by ethanol in disulfiram-treated rats were prevented or abolished in rats given 4-methylpyrazole before or after ethanol. Heart rate increased with increasing concentrations of acetaldehyde in control rats given acetaldehyde intravenously. Only a slight decrease in mean blood pressure was seen at high acetaldehyde levels (150-250 microM), whereas pulse pressure increased markedly as well as respiratory rate. At acetaldehyde levels lower than 50 microM, no effects on blood pressure were seen. The effects of acetaldehyde infusion in disulfiram-treated rats were similar to those observed in controls having comparable acetaldehyde levels. The results suggest that the disulfiram-ethanol reaction in rats is caused by the combined action of ethanol and acetaldehyde on the cardiovascular system.

The cardiovascular effects of ethanol and acetaldehyde in exercising dogs.

The cardiovascular effects of ethanol and acetaldehyde were investigated in five dogs chronically instrumented to record heart rate, left ventricular peak systolic pressure, dP/dt max, left circumflex coronary artery blood flow, coronary sinus oxygen saturation, and myocardial oxygen consumption during a regulated exercise treadmill test.

Cardiovascular effects of ethanol, its congeners and synthetic bourbon in dogs

The hemodynamic effects of ethanol, methanol, acetaldehyde, ethyl acetate, iso-amyl alcohol and synthetic bourbon were studied in anesthetized, open chest dogs. The blood levels of ethanol and congeners were measured by gas chromatography. When the blood ethanol levels were less than 3 mg/ml, heart rate, systemic arterial pressure and myocardial contractile force increased slightly. However, with higher levels of ethanol, these three parameters decreased progressively as pulmonary arterial pressure increased. Likewise, methanol, ethyl acetate, iso-amyl alcohol and synthetic bourbon depressed the cardiovascular functions with the smaller blood levels. Among the congeners studied, iso-amyl alcohol caused the most marked myocardial depressant action. Acetaldehyde always increased heart rate, systemic arterial pressure and myocardial contractile force significantly. The magnitude of the hemodynamic changes produced by synthetic bourbon was practically similar to those by synthetic ethanol when the blood ethanol levels were less than 3 mg/ml. However, with the higher doses, synthetic bourbon caused significantly greater hemodynamic changes than synthetic ethanol.