| The mechanisms of diet-induced essential hypertension are unknown. This study was designed to examine the role of a high-fat, refined-carbohydrate diet (HFS) or a low-fat, complex-carbohydrate diet (LFCC) on glucose transport, plasma insulin, blood pressure, salt-sensitivity and various parameters of nitric oxide (NO) production, including response to N-nitro-L-arginine-methyl ester (L-NAME), response to L-arginine, NO metabolite excretion, renal NOS activity, renal, aortic and cardiac inducible NOS (iNOS) and endothelial NOS (eNOS) protein content and nitrotyrosine formation. The hypotheses tested were that the HFS diet known to induce insulin resistance/hyperinsulinemia and hypertension would also cause a decrease in NO resulting in hypertension and that by switching to the LFCC diet, hypertension could be reversed, as well as all of the associated abnormalities. In as soon as 2 weeks on the HFS diet, insulin resistance and hyperinsulinemia were observed. At 2 months blood pressure was normal, however, eNOS, iNOS and nitrotyrosine were elevated in aorta, heart and kidney tissue on the HFS diet. At 6 months, renal NOS activity was elevated, and NO metabolite excretion and blood pressure were unchanged. At 2 years, eNOS, iNOS and nitrotyrosine remained elevated, NO metabolites were decreased, the increase in NOS activity was removed in the HFS and the animals were hypertensive. The HFS rats also exhibited salt-sensitivity. These results suggest that the HFS diet leads to peroxynitrite formation, thus reducing the amount of bioavailable NO leading to hypertension. Switching from the HFS to a LFCC diet normalized blood pressure and reversed all of the abnormalities associated with diet-induced hypertension. |
