Effects of long-term high-saturated and unsaturated fatty acid diets on relaxation and contraction of renal arteries in insulin resistant rats.

The present study was designed to investigate the effects of high-saturated and high-unsaturated fatty acid diets on relaxation and contraction of the renal arteries in insulin resistance (IR) rats. Wistar rats were fed normal chow diet (control), high-saturated fatty acid diet or high-unsaturated fatty acid diet for 6 months (n=14 in each group). IR was evaluated by glucose infusion rate (GIR) of hyperinsulinemic euglycemic clamp. Blood pressure was measured via the tail-cuff method. Body weight (BW), plasma total triglyceride (TG), free fatty acid (FFA), insulin, fasting blood glucose (FBG) and nitric oxide metabolite (NO2(-)/NO3(-)) were compared among the three groups. The rats were sacrificed and the renal arterial rings were placed in the physiological tissue baths for measurement of vascular response to various agents. After the arterial rings were constricted with 3 mmol/L noradrenaline (NA), endothelium-dependent vasorelaxation to acetylcholine (ACh) and endothelium-independent vasorelaxation to sodium nitroprusside (NTP) were measured. Endothelium-dependent vasorelaxation to ACh was also observed in renal arterial rings incubated with L-arginine (L-Arg), N(omega)-nitro-L-arginine (L-NNA) and methylene blue (MB), respectively. Arterial contractility was evaluated from concentration-response curves to 10 nmol/L-100 micromol/L NA. Saturated or unsaturated fatty acids led to moderate rises in blood pressure (P<0.05). It was associated with higher levels of plasma lipids and lower whole body insulin sensitivity (P<0.01). There were no significant differences in BW, FBG, TG, insulin and FFA between saturated and unsaturated fatty acid-fed rats. A decrease in endothelium-dependent vasorelaxation of the renal arteries in saturated and unsaturated fatty acid-fed rats was observed (P<0.01), but there was no marked difference between the two high-fatty acid diet groups. Endothelium-dependent vasorelaxation was increased when the arteries were incubated with L-Arg and decreased when incubated with L-NNA and MB in both high-fatty acid diet groups (P<0.05, P<0.01). But no difference was found before and after incubation with L-Arg, L-NNA and MB in the control rats. In the mean time, endothelium-independent maximal vasorelaxation response of renal arteries to NTP and renal arterial contractile responses to cumulative dose of NA were assayed, and there was no difference among the three groups (P>0.05). Endothelium-dependent vasorelaxation was negatively correlated with systolic blood pressure and TG, and positively correlated with NO2(-)/NO3(-) and GIR. There was a significantly negative correlation between FFA and NO2(-)/NO3(-). The present study suggests that both high-saturated and unsaturated fatty acid diets result in hypertension associated with significantly decreased endothelium-dependent vasorelaxation, dyslipidemia and IR, and that decreased endothelium-dependent vasorelaxation induced by high fatty acid diets is associated with impaired L-Arg-NO-cGMP pathways.