ISSN:
1432-1912
Keywords:
Vasorelaxation
;
Boldine derivatives
;
Ca2+ channel blocker
;
α1-Adrenoceptor antagonist
;
Rat aorta
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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 μmol/l (for a Ca2+ concentration of 1 mmol/1). The vasorelaxant effect on KCl-induced responses was more pronounced at 60 mmol/l KCl than at 15 mmol/1 KCI. Contraction of rat aorta in response to phenylephrine (0.01-100 μmol/l) was concentration-dependently inhibited by N-allylsecoboldine and by verapamil (3–30 μmol/l), while contraction in response to B-HT 920, serotonin or PGF2α was not affected. This relaxing effect of N-allylsecoboldine persisted in endothelium-denuded aorta. In cultured A 10 vascular smooth muscle cells, N-allylsecoboldine and verapamil displaced the binding of [3H]-prazosin (K i values = 0.4±0.2 and 0.6±0.2 μmol/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 α1-adrenoceptors.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01258470
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