Vascular Alterations in High-fat Diet-obese Rats: Role of Endothelial L-arginine/NO Pathway

Background: Mechanisms underlying vascular abnormalities in obesity remain to be completely clarified. Objective: L-arginine/nitric oxide pathway was evaluated on vascular response of high-fat diet-obese rats, focusing on endothelial and smooth muscle cells. Methods: 30-day-old rats were divided in two groups: control (C) and obese (OB, high-fat diet for 30 weeks). After 30 weeks, body weight, adiposity index, blood pressure, and metabolic and endocrine profiles of the animals were recorded. Curves to noradrenaline were obtained in absence and presence of nitric oxide synthase inhibitor (L-NAME, 3x10-4M) on intact and denuded thoracic aorta from C and OB rats. Results: Body weight, adiposity index, leptin and insulin levels were increased in OB, while blood pressure was unchanged. Obesity also produced glucose tolerance and insulin resistance. Reactivity to noradrenaline of intact aorta was similar in C and OB rats. L-NAME presence produced a similar increase in maximal responses, but a higher leftward shift of noradrenaline responses in intact aorta from C than in OB rats [EC50 (x10-7M): C=1.84 (0.83-4.07), O = 2.49 (1.41-4.38); L-NAME presence C = 0.02 (0.01-0.04)*, O = 0.21 (0.11-0.40)*†,*p < 0.05 vs respective control, †p < 0.05 vs control plus L-NAME, n = 6-7]. None of the protocols altered the reactivity to noradrenaline of denuded aortas. Conclusion: High-fat diet-induced obesity promotes metabolic and vascular alterations. The vascular alteration involve