Name: POLLYANA PEIXOTO
Publication date: 08/03/2017
Advisor:
Name |
Role |
|---|---|
| ROGER LYRIO DOS SANTOS | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| ANA RAQUEL SANTOS DE MEDEIROS GARCIA | External Examiner * |
| ROGER LYRIO DOS SANTOS | Advisor * |
| SONIA ALVES GOUVEA | Internal Examiner * |
Summary: Despite estrogen actions have been attributed to the activation of nuclear receptors (ERα and ERβ), a third estrogen receptor (G-protein-coupled estrogen receptor - GPER) has been shown to mediate the rapid action of the hormone. However, there are few studies that relate the sexual differences to the selective activation of the GPER, especially in resistance vessels, become necessary this investigation.
Wistar rats of both sexes were used in this study. Mesenteric third-order branches were isolated for the study of concentration-response curves obtained by cumulative doses of the G-1 agonist (1 nM - 10 μM) or the vehicle (DMSO) in phenylephrine-precontracted vessels. The effect of G-1 activation was evaluated before and after endothelium removal or incubation for 30 minutes with NOS and COX inhibitors (L-NAME and INDO, respectively), non-specific CYP inhibitor (clotrimazole), phosphoinositide 3-kinase (PI3k)-Akt inhibitor (LY-294,002), non-specific K+ channel blocker (TEA), specific GPER antagonist (G36) or ERα/ERβ antagonist (ICI 182,780). In addition, mesenteric resistance arteries were dissected and the protein expression of GPER, endothelial nitric oxide synthase (eNOS), catalase and superoxide dismutase (SOD) were analyzed. Moreover, we evaluated the vascular production of superoxide anion and hydrogen peroxide by fluorescence techniques, as well as the immunolocalization of the GPER.
The GPER agonist induced concentration-dependent relaxation in both sexes. There was no difference between the groups in the production of superoxide anions and hydrogen peroxide as well as in the expression of antioxidant enzymes. The protein expression of the GPER was higher in males. In the absence of the endothelium the response induced by G-1 was reduced in both groups with greater degree in the females. The immunolocalization showed greater presence of GPER in the endothelium than in vascular smooth muscle of the female rats, WHEREas there were no difference in the males rats. Vasorelaxation was attenuated in males and females in the presence of L-NAME, LY-294,002 and TEA, and this effect was similar in both groups. INDO, clotrimazole or ICI 182,780 did not reduced vasorelaxation. L-NAME + INDO results were similar to individual inhibition with L-NAME alone. There was no sex difference in protein expression and enzymatic activity of eNOS. The selectivity of the GPER agonist was confirmed in the presence of G36.
We conclude that the vascular relaxation mediated by the GPER in mesenteric resistance arteries is not influenced by sex, but partly, involve mechanisms related to the endothelial NO pathway and the activation of potassium channels.
