ABSTRACT
The vascular actions of the lipophilic gap junction inhibitors 18a-glycyrrhetinic acid, 18/3-glycyrrhetinic acid and the water-soluble hemisuccinate derivative of 18/3-glycyrrhetinic acid, carbenoxolone, were investigated in constricted rings of rabbit superior mesenteric artery. EDHF-type relaxations to acetylcholine, observed in the presence of N G -nitro-L-arginine methyl ester ( L - N A M E ) and indomethacin, were attenuated by incubation with 18a-glycyrrhetinic acid, 18/3-glycyrrhetinic acid or carbenoxolone in a concentration-dependent fashion. By contrast, none of these agents affected responses to sodium nitroprusside, an exogenous source of N O , and relaxations evoked by acetylcholine in the absence of L - N A M E were attenuated by approximately 20%. 18aglycyrrhetinic acid exerted no direct effect on vessel tone, whereas 18/3-glycyrrhetinic acid and carbenoxolone caused relaxations. Relaxations to carbenoxolone were atte nuated by endothelial denudation and by incubation with L - N A M E , whereas those to 18/3-glycyrrhetinic acid were unaffected. In conclusion, all three agents inhibit E D H F - type relaxations evoked by acetylcholine. Unlike 18a-glycyrrhetinic acid, carbenoxolone and 18/3-glycyrrhetinic acid possess intrinsic relaxing properties which in the case of carbenoxolone involves functional enhancement of N O activity in addition to direct effects on vascular smooth muscle.
