Glycyrrhetinic derivatives inhibit hyperpolarization in endothelial cells of guinea pig and rat arteries.
Glycyrrhetinic acid (GA) derivatives have been used to implicate gap junctions in vasorelaxation attributed to endothelium-derived hyperpolarizing factor (EDHF). The aim of this study was to assess whether GA compounds affect endothelial cell hyperpolarization. Membrane potentials were recorded from dye-identified endothelial and smooth muscle cells of guinea pig coronary and rat mesenteric arteries. GA derivatives had varied effects on the resting membrane potential: depolarization, hyperpolarization, or no effect, depending on the artery. 18alpha-GA (50 microM) had a small variable effect on ACh-induced hyperpolarizations in endothelial cells. 18beta-GA (30 microM) and carbenoxolone (100 microM) significantly reduced ACh-induced hyperpolarizations in both endothelial and smooth muscle cells. Smooth muscle action potentials in rat tail arteries were smaller and slower in the presence of 18beta-GA. Nerve-induced excitatory junction potentials were inhibited by 18beta-GA and carbenoxolone, whereas the time course of their decay initially increased and then decreased. In conclusion, the GA compounds had a range of effects. Their inhibition of the EDHF hyperpolarization and relaxation in the smooth muscle may stem from the inhibition of endothelial cell hyperpolarization.
Tare
Marianne
M
Department of Physiology, Monash University, Melbourne, Victoria 3800, Australia.
Coleman
H A
HA
Parkington
Helena C
HC
D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000187:drug effects*; D008638:Mesenteric Arteries / Q000502:physiology; D008839:Microelectrodes; D051381:Rats; D013623:Tail / Q000098:blood supply
D002229:Carbenoxolone; D006034:Glycyrrhetinic Acid