Influência dos hormônios sexuais masculinos sobre a reatividade vascular de artérias mesentéricas de terceira ordem: uma avaliação temporal

Abstract

Male sex hormones have been associated with a risk of cardiovascular disease, but this relationship is not fully understood. Studies that aim to elucidate the role of androgens on vascular reactivity have pointed out divergences, mainly regarding the participation of these hormones related to age. Our hypothesis is that the presence of male sex hormones, over the age, is able to impair the vascular reactivity. Therefore, the objective of this study was to make a temporal assessment of the vascular reactivity of third-order mesenteric arteries, in order to clarify the participation of androgens in the vascular function in rats. In this study Wistar rats were used and the protocols performed were previously approved by the Comissão de Ética no Uso de Animais da Universidade Federal do Espírito Santo (CEUA - UFES, number 07/2016). Eight-week-old animals were divided into Sham and orchiectomized (ORX), and were evaluated 15, 30, 60 and 75 days after surgery. Vascular reactivity was assessed in third-order mesenteric arteries. For this purpose, concentration-response curve to acetylcholine (ACh, 0.1 nM - 10 uM) it were constructed in arteries previously contracted with phenylephrine (PE, 3 uM), before and after the use of nitric oxide synthase (NOS) (Nω-nitro-L-arginine methyl ester - L-NAME 300 uM) or cyclooxygenase (COX) (indomethacin - INDO 10 uM), inhibitors individually or in combination. PE concentration-response curve (1nM - 100μM) was also performed. Nitric oxide (NO), superoxide anion (O2●-) and hydrogen peroxide (H2O2) dosages were performed on vascular tissue using fluorescent labeling with 4,5-diaminofluorescein diacetate (DAF-2DA), 2', 7' dichlorodihydrofluorescein diacetate (H2DCF-DA) and dihydroethidium (DHE), respectively. Histomorphometric analysis were performed by staining with Hematoxylin-Eosin and scanning electron microscopy in the studied arteries. Blood pressure parameters were assessed by indirect (tail plethysmography) and direct (femoral artery cannulation) measurements. The Sham-75d group showed impairment in endothelium-dependent relaxation compared to the other Sham and ORX groups. All groups studied showed a prostanoid-independent and a NO dependent vasodilatory pathway response, however this NO dependence seems to be less in the Sham-75d group. The Sham-75d group had a lower NO, and H2O2 production and a higher O2●- production. Although Sham-75d animals showed morphological and functional differences in the third-order mesenteric arteries in comparation to the other animals, there was no change in blood pressure among the studied groups over the observation period. Our data show that male sex hormones appear to play an important role in the development of vascular changes that can lead to impaired vascular reactivity in mesenteric arteries, which could be related to the onset of cardiovascular changes related to the age in males