DIVERGENT EFFECTS OF ACUTE AND CHRONIC ETHANOL EXPOSURE ON CONTRACTION AND CA2-MUSCLE CELLS( MOBILIZATION IN CULTURED VASCULAR SMOOTH)

In cultured rat vascular smooth muscle cells (VSMC), acute preincubati on of 100 mmol/L ethanol for 30 min attenuated the number of contracti ng cells in response to (10(-7) mol/L) arginine vasopressin (AVP) (P < .01). In contrast, VSMC cultured chronically for 3 days in medium sup plemented with 100 mmol/L ethanol enhanced (10(-7) mol/L) AVP-induced shape change (P < .01). Specific H-3-AVP binding to VSMC after acute o r 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-dependen t 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 Ca-45(2 +) uptake. Acute ethanol exposure inhibited and chronic ethanol admini stration enhanced Ca2+ uptake stimulated by 6 X 10(-7) mol/L Bay K 864 4, an activator of voltage-sensitive Ca2+ channels. Nifedipine, a bloc ker 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 pre exposure 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 IP, fo rmation (P < .05) and the rise in [Ca2+]i (p < .01) in response to AVP . In conclusion, the inhibitory effect of acute ethanol exposure on AV P-induced contraction in VSMC results from attenuation of receptor- an d depolarization-induced transmembrane Ca2+ uptake via voltage-sensiti ve Ca2+ channels and reduction of post-receptor PI breakdown. In contr ast, chronic ethanol exposure increases VSMC contraction in response t o AVP by enhancing Ca2+ uptake via voltage-sensitive Ca2+ channels as well as increasing IP3 formation and rise in [Ca2+]i.