Estudo dos efeitos da dieta de alta densidade energética sozinha ou combinada a bloqueadores do sistema renina angiotensina sobre os testículos de camundongos

Abstract

Hypertension is considered a risk factor for male reproductive health and has the potential to change the spermatogenesis (sperm production) and steroidogenesis (androgen production), and promote important morphological changes in the body. The aim of this study was to evaluate whether the anti-hypertensive drugs that block the renin-angiotensin system (RAS) at different levels have effects on the steroidogenesis and testicular morphology in hypertensive mice due to ingestion of a high energy density (HED) diet. Mices C57BL6 were fed a diet HED for eight weeks and then treated with aliskiren (50 mg/kg/day), enalapril (30 mg/kg/day) or losartan (10 mg/kg/day) for an additional six weeks. Blood pressure (BP) was evaluated every two weeks until the end of experiment and all animals were sacrificed by anesthetic overdose. Differences between groups were tested by one-way analysis of variance (ANOVA), followed by Holm-Sidak post-test and in all cases, the significance level was set at P ≤ 0.05. The high energy density diet led to a significant increase in BP (P < 0.05). After administration of the medication, all treatments resulted in normalization of BP. The lipidic profile of all groups fed HED diet showed a significant increase. Regarding reproductive function, there was a significant decrease in testosterone and estradiol serum levels, gene and protein expression of the aromatase enzyme, the luteinizing hormone receptor (LH-r), and steroidogenic acute regulatory protein (StAR). Furthermore, the expression of the protein angiotensin converting enzyme (ACE), receptor type 1 Ang II (AT1R) and renin were significantly decreased in the groups that received the HED diet. Among the treatments, only enalapril was able to reverse the changes. Furthermore, ACE, renin and AT1R protein expression were lower in all HED groups but the group treated with enalapril. The groups that received HED diet also presented morphological changes, and once again only enalapril could reverse these changes. As the ACE inhibitor was the only one able to reverse the hormonal and testicular morphological alterations caused by high energy density diet we could suggest that enalapril should be the drug of choice for patients who present reproductive dysfunction prior treatment.