Diet-induced changes in endothelial-dependent relaxation of the rat aorta

Purpose. Hypertension (HTN), hyperlipidemia (HLP), and hyperinsulinemia are known risk factors for the development of cardiovascular disease. Each has independently been shown to be associated with impaired endothelial functi on, as demonstrated by decreased endothelial derived relaxation (EDR). Prev ious work in our laboratory has shown that rats fed a high-fat sucrose (HFS ) diet will become insulin resistant, hypertriglyceridemic, and hypertensiv e. We hypothesize that the development of these diet-induced risk factors i s associated with endothelial dysfunction and a significant decrease in EDR . Furthermore, the endothelial dysfunction will be improved by returning to a normal (low-fat complex carbohydrate (LFCC)) diet. Methods. Adult, male Fischer rats were fed either a LFCC or a HFS diet for 6 months (n = 8 in each group). A third group of rats (SWITCH) was fed a HF S diet for 6 months and then changed to a LFCC diet for 4 weeks. Blood pres sure was measured via the tail-cuff method weekly. The rats were sacrificed and aortic ring segments were placed in physiologic tissue baths for measu rement of vascular reactivity to various agents, Arterial ring segments wer e constricted with potassium chloride (K) and phenylephrine (PE). Endotheli al-dependent vasorelaxation was measured with acetylcholine (Ach), bradykin in (BK), and calcium ionophore (CA). Endothelial-independent relaxation was measured using sodium nitroprusside (NTP). Results The HFS diet group developed HTN compared to LFCC group. Vasoconstr iction to K and PE were similar in all groups. Vasorelaxation to Ach, BK an d CA was significantly decreased in the HFS group, but returned to baseline in the diet-switched group, as did the systolic blood pressure. There were no differences in relaxation to NTP. Conclusions. HFS diet-induced HTN is associated with significantly decrease d EDR. Switching to a low-fat diet in any form reserved. reverses this effe ct. The vascular smooth muscle contraction and endothelial-independent rela xation are not affected by the diet-induced risk factors. There is a direct and reversible effect of an HFS diet on endothelial function and blood pre ssure. (C) 1999 Academic Press.