NaCl-induced hypertensive rat model of non-insulin-dependent diabetes: Role of sympathetic modulation

Systemic hypertension is common in individuals with non-insulin-dependent d iabetes (NIDD) and, in this population, markedly increases the risk for car diovascular complications. The aims of this study were to develop a rat mod el of combined NaCl-induced hypertension and NIDD, and to determine the con tribution of the sympathetic nervous system to the development of the manif est hypertension. Two-day old male Wistar-Kyoto rats were injected with eit her streptozotocin (90 mg/kg, ip; NIDD) or vehicle (citrate buffer; control ). At 4 weeks of age, the animals underwent either a right nephrectomy or a sham operation. Animals in each group were further subdivided, with one gr oup maintained on normal (0.72 %) NaCl diet whereas the other was placed on a high (8%)-NaCl diet. At 6 months of age, diabetes was confirmed by gluco se tolerance testing. Hemodynamic parameters were measured in the freely mo ving animal (ia) before and after the administration of prazosin (periphera l ai-adrenergic antagonist, iv) or clonidine (central alpha(2)-adrenergic a gonist). The NIDD rat displayed a higher (P < .05) blood glucose concentrat ion than the nondiabetic control rat during the glucose tolerance test. Ele vated dietary NaCl significantly increased mean arterial pressure (MAP) in the uninephrectomized, but not the sham-operated groups. Acute administrati on of prazosin resulted in a significantly greater reduction in MAP of both hypertensive groups than of their normotensive counterparts. Moreover, clo nidine caused a significant reduction in MAP of the hypertensive control ra t but not in the normotensive controls. By contrast, both the hypertensive NIDD and the normotensive NIDD rats showed a similar reduction in MAP in re sponse to clonidine administration. The data suggest that the combination o f uninephrectomy and dietary NaCl excess confers hypertension on the NIDD r at. Moreover, enhancement of the sympathetic pathway plays an important rol e in the regulation of arterial pressure in the hypertensive NIDD rat. (C) 2000 American Journal of Hypertension, Ltd.