Diferenças sexuais no relaxamento induzido pela progesterona em artérias mesentéricas de resistência

Abstract

Progesterone plays an important role in physiological processes related to reproductive organs, but it is already known that it can act in other systems, such as the cardiovascular system. However, little is known about its role in different vascular beds, specifically in resistance arteries. The aim of this study was to evaluate possible sex differences in progesterone-induced vasodilation in mesenteric resistance arteries in rats of both sexes. The study was approved by the Ethics Committee on the Use of Animals of the Federal University of Espirito Santo (nº 18/2020). Concentration-response curves to progesterone (10 nM-10 μM) were performed in mesenteric arteries of Wistar (10 – 12 weeks) of both sexes before and after endothelial removal or incubation with nitric oxide synthase (NOS) enzyme inhibitors ( Nω-nitro-L-arginine methyl ester - L-NAME 300 μM), cyclooxygenase (COX) (Indomethacin, INDO - 10 μM) alone or conjugated with non-selective cytochrome P450 (CYP) inhibitor (Clotrimazole, CLOT - 0.75 μM ) or a hydrogen peroxide (H2O2) degradant (Catalase, CAT - 1000 units/mL). We also evaluated the effect of nonspecific blockade of potassium channels (Tetraethylammonium, TEA - 5 mM) and the participation of the G protein-coupled estrogen receptor (GPER), using a selective GPER antagonist (G36 - 1 μM). And we investigated the participation of calcium by concentration-response curves with CaCl2 (10 µM – 30 mM) before and after incubation with progesterone (50 mM) or nifedipine (1 µM). Our results demonstrated that the acute action of progesterone promoted relaxation in mesenteric resistance arteries of male and female rats in a similar way between the sexes. This relaxation response does not appear to depend on endothelial mediators [nitric oxide (NO), prostanoids (PNs) and endothelium-dependent hyperpolarization (EDH)]. The action of progesterone appears to be more dependent of an extra-endothelial pathway in the vascular smooth muscle (VSM), with the participation of calcium, instead of potassium channels and the GPER. These findings are important for a better understanding of the vascular actions promoted by progesterone in both sexes. Moreover, it can help to understand the actions of hormonal therapies in peri and post menopause.