Medroxyprogesterone acetate does not antagonize estrogen-induced increases in endothelium-dependent vasodilation: potential clinical implications

Abstract

Objective: Determine the effect of combined 17β-estradiol benzoate (E 2) and medroxyprogesterone acetate (MPA) administration on endothelium-dependent vasorelaxation to acetylcholine (ACh). Design: Prospective, ex vivo study. Setting: Academic research laboratory. Animal(s): Mature female rats. Intervention(s): Ovariectomized rats received one of the following interventions daily for 3 days: [1] corn oil via IM injection, [2] E 2 (20 μg/kg IM), or [3] E 2 (20 μg/kg IM) and MPA (10 mg/kg IM). Main Outcome Measure(s): Basal release of nitric oxide (NO) and endothelium-dependent and endothelium-independent vasodilation from thoracic aortas obtained from each group. Result(s): Estradiol treatment potentiated the endothelium-dependent relaxation to ACh when compared with the control group. Administration of MPA with E 2 did not antagonize the beneficial effect of E 2 on endothelium-dependent relaxation. Estradiol treatment alone or in combination with MPA did not affect endothelium-independent vasodilation as compared with the case of the control group. Administration of E 2 resulted in increased basal NO release (assessed indirectly by measuring the constrictor response to N G-nitro- l-arginine [methyl ester (L-NAME)]) when compared with the case of the control group, and the addition of MPA to E 2 did not alter the effect of E 2 on basal NO release. Conclusion(s): Estradiol potentiates endothelium-dependent relaxant responses and increases basal endothelial NO release. Medroxyprogesterone acetate does not antagonize these effects of E 2.