Inhibition of the endothelium-dependent relaxation by 18beta-glycyrrhetinic acid in the guinea-pig aorta.
The effect of 18beta-glycyrrhetinic acid (GA), an agent which interferes with gap junction conductivity, on endothelium-dependent relaxation produced by substance P was investigated in isolated aortic rings of the guinea-pig. In nor-adrenaline (NA)-contracted aortic rings, substance P (10(-7) M) induced an endothelium-dependent, transient relaxation. The relaxation was only slightly reduced by the co-application of nitroarginine and diclofenac. When GA (2x10(-5) M) was applied first, it slightly reduced substance P-induced relaxation, and a subsequent co-application of nitroarginine and diclofenac strongly reduced the relaxation. In aortic rings contracted with high-K solution ([K(+)](o) = 29.4 mM), substance P-induced relaxation was reduced by the simultaneous application of GA, nitroarginine and diclofenac, but not by GA alone. In endothelium-denuded aortic rings, GA reduced the threshold concentration of NA required to produce contractions and increased the amplitude of NA-induced contractions. GA increased the amplitude of contraction produced by small increases of [K(+)](o) (<30 mM) but reduced those produced by higher concentrations of [K(+)](o) (>54 mM). In NA-contracted aortic rings, Y-26763, a K(+)-channel opener, could relax muscles with reduced amplitude in the presence of GA. It is concluded that in guinea-pig aortic rings, GA inhibits mainly the EDHF-induced components of endothelium-dependent relaxation. GA also modulated contractions produced by NA or high-K solutions. The possible effects of inhibition of gap junctions by GA on endothelium-dependent relaxation were discussed.
Fukuta
H
H
Department of Physiology, Nagoya City University Medical School, Mizuho-ku, Nagoya, 467-8601, Japan.
Koshita
M
M
Yamamoto
Y
Y
Suzuki
H
H
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D006168:Guinea Pigs; D014664:Vasodilation / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D006034:Glycyrrhetinic Acid