Acute alcohol intoxication increases the magnitude of phasic Ca2+ transients in rat mesenteric collecting lymphatics

Alcohol intoxication enhances the phasic contraction amplitude of mesenteric collecting lymphatics and decreases lymphatic myogenic tone, but the mechanisms are not known. We hypothesized that the effects of alcohol at on mesenteric lymphatic pumping and myogenic response is due to altered calcium signaling. Acute alcohol intoxication was produced by intragastric administration of 30% alcohol to conscious, unrestrained rats through surgically implanted catheters. Isovolumic administration of water (vehicle) served as control. Calcium was measured by determining the 340/380 ratio at pressure of 2 cm H 2 O and the step increases of +2 to +10 cm H 2 O). We loaded isolated mesenteric lymphatic vessels with fura‐2 to study intrinsic pump parameters. The results show that alcohol increased the amplitude of spontaneous Ca 2+ transients, compared to vehicle. Step increases in pressure caused an elevation in [Ca 2+ ] i during lymphatic diastole, that were equivalent for all pressures tested and were not different between the alcohol and vehicle groups. These results suggest that the increase in phasic contraction amplitude caused by alcohol is due to an increase in transient mobilization of Ca 2+ , but the mechanisms by which alcohol inhibits myogenic constriction may be Ca 2+ ‐independent or may involve Ca 2+ ‐sensitizing pathways. Supported by NIH P20HL018766 and a grant from the American Heart Association.