Name: ANTONIO FERREIRA DE MELO JUNIOR

Publication date: 16/04/2021
Advisor:

Namesort descending Role
NAZARE SOUZA BISSOLI Advisor *

Examining board:

Namesort descending Role
CARMEM LUIZA SARTORIO Internal Examiner *
KARLA NÍVEA SAMPAIO External Examiner *
NAZARE SOUZA BISSOLI Advisor *
SILVANA DOS SANTOS MEYRELLES Internal Examiner *

Summary: Hypertension is a relevant sex and sex hormones-dependent risk factor WHERE the cardiovascular and renal health of the population are concerned. Men experience greater losses of renal function (RF) than women, but the mechanisms remain somewhat unclear. Our goal was to evaluate the relationship between oxidative stress (OS), angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activities and RF in male and female SHR. Twelve-week-old spontaneously hypertensive rats (SHR) were submitted to either castration or SHAM surgery and divided into 4 groups, SHAM or Castrated (CAST) males or females. After 51 days we evaluated RF (inulin and sodium para-aminohippurate), ACE and ACE2 activities (fluorimetry), OS (flow cytometry), collagen deposition (picrosirius red) and protein expression (western blot). Males presented lower RF than females and castration impaired this parameter in both groups. Sexual dimorphism was not observed regarding OS and inflammation; however, castration increased this parameter more severely in males than in females. SHAM males exhibited higher collagen deposition than females, though castration increased it in both sexes, eliminating the difference. We found sexual dimorphism regarding renal ACE and ACE2 activities, which were lower in males than in females. Although castration did not alter ACE activity, it reduced ACE2 activity in females and increased it in males. Our results demonstrated that SH modulate RAS, which in turn promotes an imbalance between the oxidant/antioxidant systems in male and female SHR rats in the presence and absence of sex hormones. Severe damage to the renal function of these animals was observed, with males being the most affected by castration, tending to renal failure. Therefore, we suggest that the results found are influenced in the CAST Male group by the high activity of ACE2 and CAST Females by the imbalance between the ACE/ACE2 activity found after castration.

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