Respostas cardiovasculares mediadas pelo aumento agudo dos níveis cerebrais de angiotensina-(1-7) em animais alimentados com dieta rica em frutose

Abstract

Excessive fructose consumption and the greater exposure to stressful situations are considered risk factors that predispose the development of cardiovascular diseases. In this context, the Ang- (1-7) / receptor axis, an important endogenous mechanism that either via central or peripheral pathways, promotes important and beneficial effects, attenuating arterial hypertension, improving energy metabolism and the response to emotional stress. Several studies have pointed out the hypothalamic dorsomedial region (DMH) as a key region of the central pathways that mediate the cardiovascular responses during an alarm reaction in stress. Thus, the present study aimed at elucidate cardiovascular responses mediated by the acute increase in central levels of angiotensin- (1-7) in normal physiological conditions and in a fructose-rich diet. For this, the Wistar rats (6 weeks old) were submitted to a 10% fructose solution (FF) or drinking water (control group - CTL) for 20 weeks. At the end of the study, in an anesthetized state, the animals receive an intracerebroventricular infusion (icv) of angiotensin- (1-7) (groups A7) or sterile 0.9% saline (vehicle groups). The following were reduced: mean arterial pressure (MAP), heart rate (HR), sensitivity of heart rate control (BRS) and cardiovascular response to NMDA receptor stimulation in DMH. Statistical differences were analyzed using the one-way ANOVA test, or student test, when applicable. An Ang- (1-7) seems to act in order to improve the clinical response in the FF group (0.74 ± 0.06 vs 0.46 ± 0.09) in face of the increase in BP and improve the tachycardic response in the group of control, compared to AP (1.39 ± 0.35 vs 0.99 ± 0.28). Both FF groups that received an acute ic- infusion of Ang- (1-7) reduced the BP normalization time when compared to their CTL groups (27.0 ± 3.7 vs 75.0 ± 5.6; 66, 0 ± 8.0 vs 141.7 ± 12.2) In addition , an acute infusion of Ang- (1-7) seems to have contributed to decrease the time to reach the peak HR response in response to the BP response, in the CTL group (54.0 ± 8.1 vs 96.0 ± 8.1). The pressure and chemical response resulting from the stimulation of NMDA receptors in DMH was impaired among the groups of experiments, with no effect resulting from chronic fructose intake. Possibly the acute icv infusion of Ang- (1-7) was responsible for attenuating a pressure response in the FF-A7 group. These data suggest that the acute delivery of the peptide Ang- (1-7) centrally, promotes improvements in the baroreflex control of heart rate and that the exacerbated response to stress observed in rats chronically fed a diet rich in fructose (10 or 20 weeks; 1 and 2) due to the change in the activity of other receptors in DMH, not in NMDA.