Divergent effects of acute and chronic ethanol exposure on contraction and Ca2+ mobilization in cultured vascular smooth muscle cells.
In cultured rat vascular smooth muscle cells (VSMC), acute preincubation of 100 mmol/L ethanol for 30 min attenuated the number of contracting cells in response to (10(-7) mol/L) arginine vasopressin (AVP) (P < .01). In contrast, VSMC cultured chronically for 3 days in medium supplemented with 100 mmol/L ethanol enhanced (10(-7) mol/L) AVP-induced shape change (P < .01). Specific 3H-AVP binding to VSMC after acute or chronic exposure to 100 mmol/L ethanol did not differ from those of control experiments. Acute ethanol pretreatment attenuated basal, 10(-7) mol/L AVP-, 65 mmol/L K(+)-stimulated Ca2+ uptake, in a dose-dependent manner. In contrast, 100 mmol/L ethanol for 4 days enhanced the (P < .001) AVP- 10(-7) mol/L and (P < .01) 65 mmol/L K(+)-stimulated 45Ca2+ uptake. Acute ethanol exposure inhibited and chronic ethanol administration enhanced Ca2+ uptake stimulated by 6 x 10(-7) mol/L Bay K 8644, an activator of voltage-sensitive Ca2+ channels. Nifedipine, a blocker of these Ca2+ channels, diminished AVP-stimulated (P < .02) and K(+)-induced (P < .001) Ca2+ uptake more potently in VSMC pretreated for 4 days with 100 mmol/L ethanol than in control cells. Acute ethanol preexposure for 30 min attenuated AVP-stimulated inositol trisphosphate (IP3) formation (P < .05) and the rise in cytosolic free Ca2+ ([Ca2+]i) (P < .01). In contrast, chronic ethanol-treated VSMC enhanced IP3 formation (P < .05) and the rise in [Ca2+]i (P < .01) in response to AVP.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
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Briner
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Tsai
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Wang
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Schrier
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D002118:Calcium / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D004594:Electrophysiology; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D017483:Receptors, Vasopressin / Q000502:physiology; D013997:Time Factors
D007295:Inositol Phosphates; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000431:Ethanol; D011188:Potassium; D002118:Calcium