Mechanism of Vasorelaxation Caused by N-Benzylsecoboldine in Rat Thoracic Aorta.
The vasorelaxing effect of N-benzylsecoboldine on the rat thoracic aorta was investigated, and we also compare it with nifedipine and cromakalim. In high K(+) (60 mM) medium, Ca(2+) (0.03-3 mM)-induced vasoconstriction was inhibited concentration-dependently by N-benzylsecoboldine, whereas this contraction was not altered by cromakalim. Cromakalim relaxed aortic rings precontracted with 15 but not 60 mM of K(+). N-benzylsecoboldine and nifedipine were more potent and effective in producing relaxation in 60 mM than in 15 mM K(+)-induced contraction. N-benzylsecoboldine was found to be an alpha(1)-adrenoceptor-blocking agent in rat thoracic aorta as revealed by its competitive antagonism of phenylephrine (PE)-induced contraction (pA(2) = 6.31 +/- 0.04, pA(10) = 5.41 +/- 0.03). This relaxing effect of N-benzylsecoboldine was not antagonized by indomethacin or methylene blue, and still persisted in endothelium-denuded aorta or in the presence of nifedipine (1 &mgr;M). The increase of inositol monophosphate caused by PE in rat aorta was significantly suppressed by N-benzylsecoboldine, but not by nifedipine or cromakalim. High concentration of N-benzylsecoboldine (100 &mgr;M) did not affect the contraction induced by B-HT 920, serotonin or PGF(2alpha). Glibenclamide and charybdotoxin did not affect the relaxation of N-benzylsecoboldine in aortic rings precontracted with PE. Neither cGMP nor cAMP levels were changed by N-benzylsecoboldine. We suggest that N-benzylsecoboldine relaxes rat thoracic aorta by suppressing the Ca(2+) influx and also has antagonistic effect on alpha(1)-adrenoceptors. Copyright 1994 S. Karger AG, Basel
Teng
C.M.
CM
Pharmacological Institute and (b)School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Yu
S.M.
SM
Pan
C.P.
CP
Lee
S.S.
SS