Nitric oxide may be required to prevent hypertension at the onset of diabetes

Nitric oxide (NO) plays an important role in the regulation of vascular ton e, and evidence suggests that endothelial- dependent relaxation, possibly m ediated via NO, is impaired in diabetes. However, the role of the endotheli um in arterial pressure control early in diabetes, before dysfunction devel ops, is not known. This was evaluated in the present study by comparing the responses to induction of diabetes in vehicle-treated rats (D, n = 7) vs. rats chronically treated with N-G-nitro-L-arginine methyl ester (L-NAME; DL, n = 8). A nondiabetic group also was treated with L-NAME (L, n = 7) to c ontrol for L-NAME effects over time, independent of diabetes. After baselin e measurements, rats were given either vehicle or L-NAME (10 mu g.kg(-1).mi n(-1) iv) infusion throughout the experiment. Six days later, streptozotoci n (60 mg/kg iv) was administered, followed by a 3-wk diabetic study period. Induction of diabetes in the D+L rats caused a marked and progressive incr ease in mean arterial pressure throughout the diabetic period, averaging si milar to 70 mmHg greater than in the D rats and similar to 20 mmHg greater than in the L rats. Glomerular filtration rate and renal plasma flow tended to increase during diabetes, but this trend was reversed in the D+L rats. In addition, plasma renin activity increased in the D and D+L rats during w eek 1 of diabetes but then returned to control in the D rats, while continu ing to increase in the D+L rats. These results suggest that, in the early s tages of diabetes, NO synthesis is important to prevent hypertension from d eveloping, possibly through actions to maintain glomerular filtration and s uppress renin secretion.