Papel do sistema renina-angiotensina-aldosterona nas alterações vasculares e metabólicas induzidas pela alta ingestão de frutose em ratos

Abstract

Introduction: Chronic high fructose intake mimics the early stages of metabolic syndrome (MS), leading to progressive cardiometabolic changes. Since the reninangiotensin-aldosterone system (RAAS) is implicated in cardiovascular diseases in general, we hypothesized that treatment with enalapril and spironolactone would blunt the vascular and metabolic alterations of fructose overload. Methodology: Six-week-old male Wistar rats were assigned to receive drinking water (controls: CON) or 10% fructose solution (FRU) for 6 weeks. During the last three weeks, a sample of FRU rats received enalapril (F-ENA) or spironolactone (F-ESP). Systolic blood pressure was evaluated by tail plethysmography. Fasting glucose, insulin and glucose tolerance were measured at the end of the follow-up by strip-based glucometer. Mesenteric vascular bed reactivity was evaluated in a perfusion system. Western Blot analysis were performed for TNF-α, COX-2, SOD-1, SOD-2 and Catalase. Results: Fructose increased visceral fat without affecting body weight gain, while only enalapril prevented excessive fat accumulation and also decreased body weight. Blood pressure remained unchanged in all groups during the six weeks. FRU group had increased blood fasting glucose, which was mitigated only by spironolactone. Fructose also reduced in both glucose tolerance and insulin sensitivity, which was reverted by enalapril, while spironolactone only prevented glucose tolerance changes. FRU rats had increased vasoconstriction elicited by norepinephrine, which was fully prevented by enalapril, but not by spironolactone. Differences among the groups were maintained after nitric oxide synthase inhibition and disappeared after COX inhibition. Antioxidant defenses were affected by fructose but poorly by the treatments. Conclusions: The metabolic changes by fructose overload were accompanied by increased vasoconstriction related to constrictor prostanoids. These changes were strongly related to angiotensin-II but poorly to mineralocorticoids.