HYPERTENSION INDUCED BY NITRIC-OXIDE SYNTHESIS INHIBITION IS RENAL NERVE DEPENDENT

Recent studies have indicated that chronic administration of N-omega-n itro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (N O) synthesis, produces marked hypertension. Although the mechanism of this form of hypertension is not well understood, several studies have demonstrated that sympathetic nerve activity is at least acutely elev ated after L-NAME administration. To evaluate the potential role of th e renal sympathetic nerves in L-NAME-induced hypertension, we compared the blood pressure response to L-NAME in four groups of Sprague-Dawle y rats (n=8 each): (1) sham-operated vehicle-treated, (2) sham-operate d L-NAME-treated, (3) denervated vehicle-treated, and (4) denervated L -NAME-treated. After renal denervation or sham surgery, L-NAME was add ed to the drinking water (70 mg/100 mL) for 4 weeks, and arterial pres sure was measured weekly by the tail-cuff method. L-NAME treatment cau sed a progressive increase in arterial pressure in sham-operated rats, rising to 154+/-6 mm Hg by week 4 of treatment compared with 115 +/- 2 mm Hg in the vehicle-treated sham-operated group (P<.005). In contra st, the development of hypertension was significantly delayed and atte nuated in renal-denervated rats treated with L-NAME. The results of ou r study suggest that L-NAME-induced hypertension may be partly mediate d by or is at least dependent on the integrity of the renal nerves.