Effects of Ranolazine on Vasomotor Responses of Rat Aortic Rings

Abstract

Ranolazine is a piperazine derivative that was approved in 2006 for the treatment of chronic stable angina. Compared with first-line drugs currently used to treat angina, beneficial effects of ranolazine occur without changing hemodynamic parameters such as heart rate and blood pressure. In the present study the effects of ranolazine on vasomotor responses of rat aortic rings were examined. Pharmacological evaluation was performed by analyzing the vasomotor responses of ranolazine on aortic rings of adult male Wistar rats precontracted with phenylephrine (10(-5) M). In each experiment we used a pair of rings (with and without endothelium) from the same aorta and superfused in the same bath. Ranolazine (10(-6)-10(-4) M) induced a concentration-dependent relaxation of phenylephrine-precontracted rings. The relaxation was only partially dependent on the presence of the endothelium (56.78 ± 6.81% in rings with endothelium and 47.88 ± 4.70% in rings without endothelium). In rings with endothelium, L-NAME induced a shift to the right of the concentration-response curve to ranolazine. Blocking the cyclooxygenase pathway induced a leftward shift of the concentration relaxation curve to ranolazine in both types of rings and increased the ranolazine-induced relaxation in rings without endothelium. Ranolazine has a vasodilatory effect that is predominantly endothelium-independent. The synthesis/release of nitric oxide by the endothelium may, however, contribute to its relaxing action. These effects of ranolazine may contribute to its beneficial effects in patients with stable angina.