Name: IZABELA MOREIRA BONFIM

Publication date: 21/12/2022
Advisor:

Namesort descending Role
ROGER LYRIO DOS SANTOS Advisor *

Examining board:

Namesort descending Role
ALESSANDRA SIMAO PADILHA Internal Examiner *
NATHALIE TRISTÃO BANHOS DELGADO DE LIMA External Examiner *
ROGER LYRIO DOS SANTOS Advisor *

Summary: 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 of normotensive 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 toprogesterone (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-selectivecytochrome 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 potassiumchannels (Tetraethylammonium, TEA -5 mM). And we investigated the participation of calcium byconcentration-response curves with CaCl2(10 μM –30 mM) before and after incubation with progesterone (50 mM) and nifedipine (1 μM). Our results demonstrated that the acute action of progesterone promoted relaxation in mesenteric resistance arteries of normotensive male and female rats in a similar way between the sexes. Thisrelaxation response does not appear to depend on endothelial mediators (NO, PNs, EDH). The action of progesteroneappearsto be more dependentof an extra-endothelial pathway in thevascular smooth muscle (VSM), with the participation of calcium,instead ofpotassiumchannelsand the G protein-coupled estrogen receptor (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.

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