Oral contraceptive administration attenuates endothelium-dependent relaxation in response to histamine but not to acetylcholine in aortic rings of female rats

Abstract

The incidence of vascular disorders is markedly lower in cycling, pre-menopausal women and post-menopausal women receiving estrogen-progestogen therapy than in men or untreated postmenopausal women. Clinical studies demonstrate that estrogenprogestogen therapy in pre-menopausal women is associated with increased arterial vascular risk. However, the mechanism of estrogen-progestogen therapy in arterial vascular complications remain unclear. Therefore, the present study aimed at investigating whether chronic administration of combined oral contraceptive (OC) containing progestogen with androgenic property alters endothelium-dependent relaxation responses of the aorta to histamine and acetylcholine. The experiments have been studied on aortic rings obtained from vehicle-treated and OC-treated female Sprague-Dawley rats. Isometric reactivity of aortic rings was recorded with a strain gauge transducer. The maximum contractile response of the aortic rings to noradrenaline in the OC-treated group was not significantly different from that in the vehicle-treated group. Both acetylcholine and histamine caused relaxation of the noradrenaline pre-contracted aortic rings. The relaxation response to acetylcholine in rings from vehicle-treated and OC-treated rats did not differ significantly, while relaxation response to histamine was significantly attenuated in aortic rings from OC-treated rats. In conclusion, the results from the present study suggest that the increased arterial vascular risk associated with OC administration might involve altered endothelium-dependent relaxation via histaminergic-mediated mechanism, but not via muscarinergic-mediated mechanism.