Beneficial vs. detrimental actions of ethanol on heart and coronary vascular muscle: roles of Mg2+ and Ca2+.
Epidemiologic studies suggest that daily ingestion of small amounts of alcohol may protect the heart, whereas higher intake may be detrimental. We studied: 1) cardiac performance, bioenergetics, and [Mg2+]i of isolated working rat hearts during perfusion with Krebs-Henseleit medium containing different concentrations of ethanol (EtOH), 2) mechanical responses. Ca2+ metabolism and Mg content of isolated coronary arteries obtained from dogs, sheep, and piglets subjected to varying concentrations of EtOH and [Mg2+]o and 3) intracellular free Ca2+ of isolated rat cardiac myocytes. In intact hearts, EtOH produced a biphasic hemodynamic change, depending upon concentration; 15 mM EtOH (0.07 g/dl) and 45 mM EtOH (0.21 g/dl) were stimulatory: 90 (0.42 g/dl), 135 (0.63 g/dl), and 170 mM (0.79 g/dl) EtOH were depressive. EtOH 15 and 45 mM increased coronary flow up to 150%, cardiac output up to 130%, stroke volume up to 135%, and oxygen consumption (VO2) up to 130%. However, 90 mM and higher EtOH depressed most hemodynamic parameters (except for heart rate) dose dependently. Lactic acid, lactic acid dehydrogenase, and creatine phosphokinase levels in the perfusate tended to be elevated progressively with increasing duration of EtOH perfusion and pH tended to be reduced (p < 0.05). [31P]NMR spectroscopy on hearts revealed that EtOH > or = 90 mM resulted in rises in Pi/ATP concentration ratio with no significant change in PCr/ATP ratio; [Mg2+]i levels fell and cytosolic pH tended to become slightly acidotic [19F]NMR spectroscopy of isolated myocytes revealed that [Ca2+]i rises at high concentrations of EtOH. With respect to coronary vascular muscle (CVM), low concentrations of EtOH resulted in a concentration-dependent reduction in contractions induced by K+, angiotensin II, and 5-HT; concentration-effect curves were shifted rightward to higher concentrations. Low [Mg2+]o potentiated contractions of CVM induced by EtOH. Low EtOH also resulted in reductions in exchangeable and membrane-bound 45Ca in CVM; medium to high concentrations of EtOH reduced Mg content in CVM and increased 45Ca. In the absence of [Ca2+]o, caffeine and EtOH induced similar, transient contractions followed by relaxation in K(+)-depolarized coronary arterial tissues. EtOH-induced contractions were completely abolished by pretreatment of tissues with caffeine. These results on isolated coronary vessels suggest that in addition to a need for [Ca2+]o, an intracellular release of Ca2+ is needed for EtOH to induce contractions. Overall, the data indicate that low concentrations of EtOH (15, 45 mM) are beneficial on cardiac performance, at least in the intact rat heart and coronary arteries: higher concentrations of EtOH (90, 135 mM) are detrimental. High concentrations of EtOH decrease coronary flow, lead to loss of cellular Mg2+, hypoxia, metabolic acidosis of the myocardium, cell membrane damage, and Ca2+ overload, which could result in cardiac failure. Cellular loss of Mg2+ appears to be causative in the detrimental actions of EtOH on the heart.
Department of Physiology, State University of New York, Brooklyn 11203, USA.
B M
BM
Altura
L Y
LY
Zou
B T
BT
Altura
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L
Jelicks
B A
BA
Wittenberg
R K
RK
Gupta
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012756:Sheep; D013552:Swine
D002492:Central Nervous System Depressants; D000431:Ethanol; D008274:Magnesium; D002118:Calcium