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Comparison of alpha and beta isoforms of glycyrrhetinic acid and carbenoxolone as inhibitors of EDHF-type relaxation

Chaytor, A.T., Marsh, W. L., Hutcheson, Iain Richard and Griffith, Tudor Morley 2001. Comparison of alpha and beta isoforms of glycyrrhetinic acid and carbenoxolone as inhibitors of EDHF-type relaxation. Presented at: Third International Symposium on Endothelium-Derived Hyperpolarizing Factor, Vaux de Carnay, France, 14-16 June 2000. Published in: Vanhoutte, P. M. ed. EDHF 2000. London: Taylor and Francis, pp. 115-126.

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The vascular actions of the lipophilic gap junction inhibitors 18alpha-glycyrrhetinic acid, 18beta-glycyrrhetinic acid and the water-soluble hemisuccinate derivative of 18beta-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-NAME) and indomethacin, were attenuated by incubation with 18alpha-giycyrrhetinic acid, 18beta-glycyrrhctinic acid or carbenoxolone in a concentration-dependent fashion. By contrast, none of these agents affected responses to sodium nitroprusside, an exogenous source of NO, and relaxations evoked by acetylcholine in the absence of L-NAME were attenuated by approximately 20%. 18alpha-glycyrrhetinic acid exerted no direct effect on vessel tone, whereas 18beta-glycyrrhetinic acid and carbenoxolone caused relaxations. Relaxations to carbenoxolone were attenuated by endothelial denudation and by incubation with L-NAME, whereas those to 18beta-glycyrrhetinic acid were unaffected. In conclusion, all three agents inhibit EDHF-type relaxations evoked by acetylcholine. Unlike 18alpha-glycyrrhetinic acid, carbenoxolone and 18beta-glycyrrhetinic acid possess intrinsic relaxing properties which in the case of carbenoxolone involves functional enhancement of NO activity in addition to direct effects on vascular smooth muscle

Item Type: Conference or Workshop Item (Paper)
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Taylor and Francis
ISBN: 9780415269049
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Last Modified: 04 Jun 2017 04:04

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