A mechanism of vasodilatory action of polyamines and acetylpolyamines: possible involvement of their Ca2+ antagonistic properties.

Polyamines, a class of low-molecular weight organic polycations, have been shown to produce relaxing effects in vascular smooth muscles, although the mechanism has not been carefully examined. In this study, the mechanism of vascular action of polyamines and their metabolites, acetylpolyamines, was pharmacologically examined in the rabbit isolated thoracic aorta focusing on an endothelium-dependent component of vasodilatation and Ca 2+ influx through plasma membrane channels. Both polyamines and acetylpolyamines (except N 1 -acetylputrescine, which produced no response or very slight contraction) caused concentration-dependent relaxation in preconstricted aortic rings containing an intact endothelium. Aortic rings denuded of endothelium were also responsive to both polyamines and acetylpolyamines. Inhibitors of nitric oxide (reduced haemoglobin and N ω -nitro-L-arginine methyl ester), vasodilator prostaglandins (indomethacin) and guanylyl cyclase (methylene blue) did not affect the relaxation induced by both polyamines and acetylpolyamines in either endothelium-intact or -denuded aortic rings. Both polyamines and acetylpolyamines inhibited the concentration-dependent contraction for phenylephrine and K + . The Ca 2+ agonist Bay K 8644 induced concentration-dependent contraction in segments of rabbit aorta partially depolarized with 15 mM KCI, and both polyamines and acetylpolyamines relaxed the Bay K 8644-induced contraction in a concentration-dependent manner. Interestingly, both polyamines and acetylpolyamines also decreased contractions evoked by the Ca 2+ ionophore A23187. The concentration-response curve to exogenous Ca 2+ in K + -depolarization medium (K + = 120 mM) was shifted to the right by both polyamines and acetylpolyamines. The response elicited by Ca 2+ was increased by Bay K 8644 (10 -6 M), and this potentiation was also inhibited by both polyamines and acetylpolyamines. The results indicate that both polyamines and acetylpolyamines can induce vaso-relaxation of rabbit thoracic aorta by an endothelium-independent mechanism in-vitro and relax vascular smooth muscle by acting at the plasma membrane level, decreasing the influx of Ca 2+ . Therefore, polyamines and acetylpolyamines may have Ca 2+ antagonistic properties which may, in part, be involved in the mechanism of rabbit aortic vascular smooth muscle relaxation.