Effect of inhibition of nitric oxide synthase on blood pressure and renal sodium handling in renal denervated rats

The role of sympathetic nerve activity in the changes in arterial blood pre ssure and renal function caused by the chronic administration of N-G-nitro- L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthes is, was examined in sham and bilaterally renal denervated rats. Several stu dies have demonstrated that sympathetic nerve activity is elevated acutely after L-NAME administration. To evaluate the role of renal nerve activity i n L-NAME-induced hypertension, we compared the blood pressure response in f our groups (N = 10 each) of male Wistar-Hannover rats weighing 200 to 250 g : 1) sham-operated vehicle-treated, 2) sham-operated L-NAME-treated, 3) den ervated vehicle-treated, and 4) denervated L-NAME-treated rats. After renal denervation or sham surgery, one control week was followed by three weeks of oral administration of L-NAME by gavage. Arterial pressure was measured weekly in conscious rats by a tail-cuff method and renal function tests wer e performed in individual metabolic cages 0, 7, 14 and 21 days after the be ginning of L-NAME administration. L-NAME (60 mg kg(-1) day(-1)) progressive ly increased arterial pressure from 108 +/- 6.0 to 149 +/- 12 mmHg (P<0.05) in the sham-operated group by the third week of treatment which was accomp anied by a fall in creatinine clearance from 336 +/- 18 to 222 +/- 59 mu l min(-1) 100 g body weight(-1) (P<0.05) and a rise in fractional urinary sod ium excretion from 0.2 +/- 0.04 to 1.62 +/- 0.35% (P<0.05) and in sodium po st-proximal fractional excretion from 0.54 +/- 0.09 to 4.7 +/- 0.86% (P<0.0 5). The development of hypertension was significantly delayed and attenuate d in denervated L-NAME-treated rats. This was accompanied by a striking add itional increase in fractional renal sodium and potassium excretion from 0. 2 +/- 0.04 to 4.5 +/- 1.6% and from 0.1 +/- 0.015 to 1.21 +/- 0.37%, respec tively, and an enhanced post-proximal sodium excretion compared to the sham -operated group. These differences occurred despite an unchanged creatinine clearance and Na+ filtered load. These results suggest that bilateral rena l denervation delayed and attenuated the L-NAME-induced hypertension by pro moting an additional decrease in tubule sodium reabsorption in the post-pro ximal segments of nephrons. Much of the hypertension caused by chronic NO s ynthesis inhibition is thus dependent on renal nerve activity.