Excess dietary glucose alters renal function before increasing arterial pressure and inducing insulin resistance

BACKGROUND: Diets high in carbohydrates are associated with hypertension, activation of the renin-angiotensin system, hyperinsulinemia, insulin resistance, and renal dysfunction. This study tests the hypothesis that the initial effect of a long-term high carbohydrate diet is a renin-angiotensin system dependant impairment of renal function. METHODS: Three-week-old male Sprague-Dawley rats drank water containing 5% glucose or water alone. Four weeks later, arterial pressure was continuously recorded in conscious restrained rats. Urine and blood samples were collected by catheter before, during, and after intravenous saline infusion, and fasting glucose tolerance tests were performed to estimate insulin resistance. To assess the possible role of the renin-angiotensin system, a group of glucose-fed rats was treated with oral captopril for 2 days before the renal function study. RESULTS: Despite slightly and significantly lowered body weight, the treatments did not significantly alter heart and kidney weights, arterial pressure, or heart rate. Non-fasting blood sugar levels were slightly higher in the two groups of glucose-fed rats compared with the control rats (P < .05), but fasting blood sugar concentration and glucose tolerance were not significantly different among groups. The glucose-fed rats displayed significantly impaired renal diuresis and natriuresis as well as significantly elevated glomerular filtration rate and filtration fraction, but administration of captopril corrected these impairments. Effective renal blood flow and renal vascular resistance were not significantly different among groups. CONCLUSIONS: These results indicate that diets high in carbohydrates impair renal function before they increase arterial pressure, and that this effect is dependent on an intact renin-angiotensin system.