Vasorelaxant effect of ranolazine on isolated normal and diabetic rat aorta: A study of possible mechanisms

摘要

Ranolazine, an antianginal drug, acts through blocking the cardiac late sodium channels and/or inhibition of fatty acids beta-oxidation. While its cardiac action has been studied extensively, few studies have focused on its vascular effects. In the present study, the vasodilatory effect of ranolazine on isolated rat aorta in normal and diabetic rats has been studied. Methods: The effect of cumulative concentrations of ranolazine on aortic rings precontracted with phenylephrine, calcium and KCl (40 and 100 mM; in the absence and presence of glibenclamide) were studied and its potency and maximum relaxant effects were calculated. Results: Ranolazine relaxed the phenylephrine and calcium induced contractions in both the normal and diabetic aortas. It also relaxed the contractions induced by both low and high concentrations of KCl. Preincubation of the tissues with glibenclamide had no effect. The potency and maximum effect of ranolazine did not differ significantly between the normal and diabetic rings except when the tissues were contracted by calcium in which ranolazine showed greater potency toward normal tissues. Conclusion: It is concluded that ranolazine could relax the aortic contractions in both normal and diabetic states. It seems that both blockade of alpha-adrenergic receptors and voltage-operated calcium channels contribute to this effect.