Mechanisms of vasorelaxation induced by N-allylsecoboldine in rat thoracic aorta.

N-Allylsecoboldine was shown to be the most effective of several boldine derivatives that were tested for their vasorelaxing effect on the rat aorta. In KCl (60 mmol/l) medium, Ca2+ (0.03-3 mmol/l)-induced vasoconstriction was inhibited, concentration-dependently, by N-allylsecoboldine. The IC50 for N-allylsecoboldine was calculated to be about 4 mumol/l (for a Ca2+ concentration of 1 mmol/l). The vasorelaxant effect on KCl-induced responses was more pronounced at 60 mmol/l KCl than at 15 mmol/l KCl. Contraction of rat aorta in response to phenylephrine (0.01-100 mumol/l) was concentration-dependently inhibited by N-allylsecoboldine and by verapamil (3-30 mumol/l), while contraction in response to B-HT 920, serotonin or PGF2 alpha was not affected. This relaxing effect of N-allylsecoboldine persisted in endothelium-denuded aorta. In cultured A10 vascular smooth muscle cells, N-allylsecoboldine and verapamil displaced the binding of [3H]-prazosin (Ki values = 0.4 +/- 0.2 and 0.6 +/- 0.2 mumol/l, respectively). The increase of inositol monophosphate caused by phenylephrine in rat aorta was completely suppressed by chloroethylclonidine, but only slightly inhibited by N-allylsecoboldine and by verapamil. Glibenclamide or charybdotoxin did not affect the relaxation induced by N-allylsecoboldine of aortic rings precontracted with phenylephrine. Neither the cGMP nor the cAMP content was changed by N-allylsecoboldine. We conclude that N-allylsecoboldine relaxes the rat aorta by blocking Ca2+ channels and that it also has an antagonistic effect at alpha 1-adrenoceptors.