Effects of ethanol administration at a high-dose level on the stimulatory action by bradykinin in vascular permeability.

The effects of ethanol (EtOH) administration at a high-dose level on the stimulatory action by bradykinin in vascular permeability were examined in rats, as compared with the effects of histamine and hyaluronidase. Oral administration (7.5 g/kg) and intraperitoneal injection (5 g/kg) of EtOH markedly potentiated the vascular permeability accelerated by bradykinin, but they suppressed in reverse such effects induced by histamine and hyaluronidase. EtOH did not affect the stimulatory action of bradykinin on the vascular permeability when intracutaneous injection was done under the coexistence with bradykinin. The blood pressure was found to descend 30 min later, though there was a transient rise immediately after the oral administration of EtOH (7.5 g/kg). The oral administration of EtOH (7.5 g/kg) caused no change in both enzyme activities of aspartic acid aminotransferase and alanine aminotransferase in blood for 3 h. The intraperitoneal injection of EtOH (5 g/kg) lowered the blood bradykinin level and increased the blood hyaluronidase activity. In vitro, EtOH elicited a concentration-dependent increase in the kallikrein activity, trypsin activity, and bradykinin-decomposed activity in plasma. These results strongly suggest that vascular permeability results from elevation in the bradykinin level, direct action of EtOH on inflamed skin site, and actions of EtOH or its metabolites on bradykinin-regulator, which involves bradykinin receptor and NO and endothelin productions.