TEMPORAL INFLUENCE OF THE RENAL NERVES ON RENAL EXCRETORY FUNCTION DURING CHRONIC INHIBITION OF NITRIC-OXIDE SYNTHESIS

To determine whether the sympathetic nervous system contributes to the hypertension induced by long-term suppression of nitric oxide synthes is, we determined the neurally induced changes in renal excretory func tion during chronic administration of NG-nitro-L-arginine methyl ester (L-NAME). Studies were carried out in six conscious chronically instr umented dogs subjected to unilateral renal denervation and surgical di vision of the urinary bladder into two hemibladders to allow separate 24-hour urine collection from denervated and innervated kidneys. Anima ls were studied during acute (100 minutes) and chronic (5 days) intrav enous infusion of L-NAME at 37.1 nmol/kg per minute (10 mu g/kg per mi nute). During the first 100 minutes of L-NAME, there were no significa nt changes in mean arterial pressure (control: 96 +/- 3 mm Hg), but he art rate fell from 66 +/- 6 to 55 +/- 7 beats per minute. Changes in g lomerular filtration rate were not significant, but renal plasma flow and urinary sodium excretion decreased to approximate to 75% and 50% o f control values, respectively; however, these changes were comparable in both kidneys. In association with these responses, plasma concentr ations of norepinephrine (control: 887 +/- 130 pmol/L or 150 +/- 22 pg /mL) and epinephrine (control: 691 +/- 192 pmol/L or 108 +/- 30 pg/mL) tended to decrease. In contrast to the acute re sponses, mean arteria l pressure increased from 92 +/- 3 to 106 +/- 3 mm Hg and heart rate d ecreased from 72 +/- 4 to 57 +/- 5 beats per minute by day 5 of L-NAME infusion, while renal plasma flow and glomerular filtration rate were not significantly different from control values. Most importantly, th ere were no significant differences in urinary sodium excretion betwee n innervated (control: 31 +/- 2 mmol/d) and denervated (control 33 +/- 2 mmol/d) kidneys during chronic L-NAME infusion or during the recove ry period. These results indicate that the renal sympathetic nerves do not play an important role in promoting sodium retention during eithe r acute or chronic inhibition of nitric oxide synthesis in conscious d ogs. Thus, increased renal sympathetic nerve activity does not contrib ute significantly to L-NAME-induced hypertension.