Efeitos sexo-dependentes da exposição crônica ao cádmio sobre a reatividade vascular de ratos

Abstract

Introduction: Exposure to Cd is associated with several cardiovascular diseases, such as atherosclerosis and arterial hypertension, probably by inducing oxidative stress and vascular dysfunction. Cardiovascular diseases are the major causes of death in the world and the higher prevalence in men increased the possibility of women of childbearing age to present a protection of the cardiovascular system, probably due to the action of female sex hormones. As studies of the effects of Cd on the vasculature were carried out in males, it is not known whether females would have vascular function affected by exposure to this metal. Objective: To analyze the effects of chronic exposure to 100 ppm cadmium chloride on the vascular function of male and female Wistar conductance arteries. Material and Methods: The experiments were performed on 3-month-old male and female Wistar who received cadmium chloride (CdCl2 100 mg/L in drinking water for 30 days) or vehicle (filtered water). Before the start of exposure and at the end of it, data on systolic blood pressure and weight of the animals were recorded. After 30 days of exposure to the metal, the animals were euthanized and blood was collected for the dosage of cadmium and estrogen, and thoracic aorta, for the evaluation of vascular reactivity. Results: Wistar females exposed to Cd had a reduction in weight gain and systolic blood pressure did not change significantly after exposure to the metal. No difference was found in estrogen dosage between control and cadmium-exposed rats. In the analysis of myeloperoxidase (MPO) an increase in the activity of this enzyme was found in both groups exposed to the metal. Exposure to cadmium produced a concentration of the metal in the blood of 2.89 µg/L against 0.27 µg/L found in unexposed females, in males an increase in the concentration of the metal was observed in relation to females, exposed males had 4, 7 µg/L and unexposed 0.3 µg/L. There was no change in the vascular response to Phenylephrine (Fe), Acetylcholine (ACh) and Sodium Nitroprusside (NPS) in females, however males had changes in ACh and Fe curves. Incubation with L-NAME shifted the concentration-response curve to Fe in both groups, but this effect was smaller in males exposed to Cd, suggesting reduced nitric oxide bioavailability. In addition, incubation with apocynin and catalase reduced the response to Fe in males exposed to Cd, suggesting the release of superoxide anion and hydrogen peroxide, respectively. Conclusion: The results of the present study demonstrate that exposure for 30 days to Cd produces an increase in blood pressure and vascular changes in males, but not in females, suggesting that the cardiovascular abnormalities induced by the metal are sex-dependent.