DECREASED RENAL NITRIC OXIDE SYNTHASE PRECEDES HYPERTENSION AND RESULTS IN SODIUM SENSITIVITY

Abstract

1673 Although the etiology of diet-induced essential hypertension is unknown, recent evidence suggests that defects in nitric oxide production may play a role. We recently demonstrated (J. Appl. Physiol. 84: 1311-1315, 1998) that a high-fat, refined-carbohydrate diet (HFS) increases both serum insulin and systolic blood pressure. In the present study, we investigated whether defects in renal nitric oxide production play a role in diet-induced hypertension, and whether this dysfunction is a cause or a consequence of hypertension. Female Fischer rats (n=8) were placed on either the HFS or a low-fat, complex-carbohydrate diet (LFCC) diet for a period of 18 months and blood pressure and renal endothelial NO synthase (eNOS) protein expression were analyzed. At 18 months on the diet, both groups were placed on a high salt (4%) diet for a period of one week and the blood pressure measured. For one additional week, the LFCC group was given Nω-nitro-L-arginine methyl ester (L-NAME) in the drinking water (.5 mg/ml) while on the high salt diet and the blood pressure measured. The blood pressure was not significantly elevated until 12 months on the diet, and at 18 mo on the diet, the HFS rats were hypertensive (147.3±3.7 vs. LFCC, 123.0±3.9 mmHg, systolic pressure, P<0.01). After exposure to the high salt diet, blood pressure increased in the HFS animals (160.0±4.1, P<0.01 vs HFS) with no effect in the LFCC (123.8±4.7), but was significantly elevated when L-NAME was added with salt in the LFCC (157.0±3.9, P<0.001). Immunoblots performed on whole kidney homogenates after 6 mo on the diets demonstrated a decrease in eNOS protein expression in the HFS which was decreased no further at 18 mo. These results demonstrate that: 1) a high-fat, refined-sugar diet causes hypertension, 2) this diet decreases eNOS protein expression 3) the decrease in NOS protein precedes the development of hypertension, and thus is a cause, rather than a consequence, of hypertension, 4) the decrease in renal NOS production may be the cause of increased sensitivity to a high-salt diet. Supported by NIH Grant AG 07592