Diet-Induced Changes in Endothelial-Dependent Relaxation of the Rat Aorta

Abstract

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 function, as demonstrated by decreased endothelial derived relaxation (EDR). Previous work in our laboratory has shown that rats fed a high-fat sucrose (HFS) diet will become insulin resistant, hypertriglyceridemic, and hypertensive. We hypothesize that the development of these diet-induced risk factors is 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 HFS diet for 6 months and then changed to a LFCC diet for 4 weeks. Blood pressure was measured via the tail-cuff method weekly. The rats were sacrificed and aortic ring segments were placed in physiologic tissue baths for measurement of vascular reactivity to various agents. Arterial ring segments were constricted with potassium chloride (K) and phenylephrine (PE). Endothelial-dependent vasorelaxation was measured with acetylcholine (Ach), bradykinin (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. Vasoconstriction to K and PE were similar in all groups. Vasorelaxation to Ach, BK, and 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 decreased EDR. Switching to a low-fat diet reverses this effect. The vascular smooth muscle contraction and endothelial-independent relaxation 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 pressure.