Renal nerves are required for hypertension at the onset of diabetes in L‐NAME treated rats

When diabetes is induced in rats that have NO synthesis blocked chronically, MAP increases significantly, and we have shown that chronic i.v infusion of α1 and β-adrenergic receptor antagonists attenuates the hypertension. This study was designed to determine the role of the renal sympathetic nerves in mediating the increase in blood pressure in uninephrectomized control (C)and denervated (D) rats. Rats in either group were pretreated with vehicle (C; n=3 and D; n=3) or L-NAME (C+L; n=3 and D+L; n=4) for ~7 days and then STZ was administered to mark the beginning of 2 weeks of Type I diabetes. Baseline MAP in C and D rats averaged 96±0.7 and 90±0.3 mmHg, and there was no change in MAP during diabetes. However, as we have shown in previous studies, MAP progressively increased at onset of diabetes in L-NAME treated rats (C+L), from the L-NAME baseline of 125±2.6 mmHg to 145±4.3 and 173±13.0 mmHg during diabetic weeks 1 and 2, respectively. Denervation lowered the L-NAME baseline to 108±0.8 mmHg and prevented the diabetes induced hypertension, with MAP averaging 112±1.5 and 120±3.2 mmHg, respectively, during diabetic weeks 1 and 2. Glomerular filtration rate (GFR) increased at the onset of diabetes in the C and D groups and this response was prevented in rats treated with L-NAME, as we have reported, and denervation prevented that effect. These data suggest that renal sympathetic activity plays an important role in the hypertensive response to the onset of diabetes in the absence of NO, and this effect is consistent with the role of renal vascular resistance and ANGII that we have reported.