Impaired saline-stimulated diuresis and natriuresis in the conscious hypertensive glucose-intolerant rat

Background: A major complication of type 2 diabetes is renal dysfunction, a condition that worsens with coexistence of systemic hypertension. However, less is known regarding the renal impact of the prediabetic condition characterized by glucose intolerance. Therefore, we tested the hypothesis that chronic glucose intolerance leads to abnormal renal function, a condition also exacerbated by concurrent systemic hypertension. Methods: A rat model of concomitant NaCl-sensitive hypertension and glucose intolerance was used to study renal function. Glucose intolerance was produced by administering streptozotocin to neonatal Wistar-Kyoto rats, and systemic hypertension was induced by combining dietary NaCl excess with unilateral nephrectomy. Hemodynamic and renal excretory responses were determined in conscious animals before and after administration of a 30-min isotonic saline challenge (5% of body weight, intravenously). Results: Nine-month-old glucose-intolerant rats fed a normal NaCl diet did not manifest impairment in saline-stimulated diuresis and natriuresis. By contrast, 3-month-old glucose-intolerant rats fed a high NaCl diet displayed an exaggerated diuretic and natriuretic response to a saline challenge. Although saline-stimulated diuresis and natriuresis were enhanced in the hypertensive rats, they were reduced in the hypertensive glucose-intolerant animals. The reduction in renal excretory function of the latter group was caused by alterations in both glomerular function and tubular reabsorption of fluid and sodium. Conclusions: The coexistence of systemic hypertension and glucose intolerance result in impaired renal excretory function. This defect could be important, as hypertension can develop before the onset of overt type 2 diabetes.