Ethanol effects on vascular smooth muscle of human umbilical artery

IVELI F, SALEMME S, REBOLLEDO A, GENDE A, MILESI V.

Mar del Plata - Bs. As. Argentina

Congreso; XXXIII Reunión Anual de la Sociedad Argentina de Biofísica – Congreso Conjunto de Sociedades Biomédicas; 2004

Contracile and relaxant effects of ethanol have been described in different blood vessels. In this study we investigated ethanol effects on isometric force development in human umbilical artery (HUA) rings. Moreover, using the patch clamp technique, we tested ethanol effects on Ca2+ currents in isolated HUA smooth muscle cells. About 75 % of the studied segments (n=64) developed an active and stable contraction when initially stretched to 2 gF. In these rings ethanol (100 and 200 mM) produced a relaxation of this contraction in a dose-independent manner (-20.2±7.3 n=7, p<0.05 and –31.3±11.0 gF/gW n=7, p<0.05 by ANOVA, respectively). The same ethanol doses tested on rings preincubated with L-NAME and indomethacin (inhibitors of the synthesis of the relaxant factors NO and prostacyclin, respectively) failed to produce relaxation (3.2±7.1 and –1.1±3.2 gF/gW n=7, p<0.05 vs. non preincubated). In both groups, addition of a high-K+ (80 mM) depolarizing solution evoqued a contraction whose maximal value was dependent on ethanol concentration (96.2±17.3 n=11 and 70.4±14.8 gF/gW n=9, p<0.05) which was unaffected by L-NAME and indomethacin (by ANOVA vs non preincubated). The washing of ethanol significantly increased contractile force both in non-preincubated rings (41.9±15.3 and 106.4±33.4 % of augmentation, p<0.05) and in preincubated ones (18.5±3.3 and 62.7±15.9 % of augmentation, p<0.05). In serotonin (1 µM) stimulated rings ethanol (200 mM) also produced vascular relaxation (112.6±36.4 % n=8, p<0.05). In isolated smooth muscle cells ethanol (100 mM) inhibited L-type Ca2+ current (55.4±16.1 % of inhibition measured at +20 mV, n=3 p<0.05). We conclude that in HUA ethanol relaxes basal tone and depresses contractions induced by high extracellular K+ and serotonin. The results suggest that NO and prostacyclin as well as inhibitory effects on L-type Ca2+ channels participate in ethanol relaxant mechanism.