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 synthesis, we determined the neurally induced changes in renal excretory function during chronic administration of NG-nitro-L-arginine methyl ester (L-NAME). Studies were carried out in six conscious chronically instrumented dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into two hemibladders to allow separate 24-hour urine collection from denervated and innervated kidneys. Animals were studied during acute (100 minutes) and chronic (5 days) intravenous infusion of L-NAME at 37.1 nmol/kg per minute (10 micrograms/kg per minute). During the first 100 minutes of L-NAME, there were no significant changes in mean arterial pressure (control: 96 +/- 3 mm Hg), but heart rate fell from 66 +/- 6 to 55 +/- 7 beats per minute. Changes in glomerular filtration rate were not significant, but renal plasma flow and urinary sodium excretion decreased to approximately 75% and 50% of control values, respectively; however, these changes were comparable in both kidneys. In association with these responses, plasma concentrations 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 responses, mean arterial pressure increased from 92 +/- 3 to 106 +/- 3 mm Hg and heart rate decreased 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, there were no significant differences in urinary sodium excretion between innervated (control: 31 +/- 2 mmol/d) and denervated (control 33 +/- 2 mmol/d) kidneys during chronic L-NAME infusion or during the recovery period. These results indicate that the renal sympathetic nerves do not play an important role in promoting sodium retention during either acute or chronic inhibition of nitric oxide synthesis in conscious dogs. Thus, increased renal sympathetic nerve activity does not contribute significantly to L-NAME-induced hypertension.
Reinhart
G A
GA
University of Mississippi Medical Center, Department of Physiology and Biophysics, Jackson, MS 39216-4505, USA.
Lohmeier
T E
TE
Mizelle
H L
HL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects / Q000294:innervation*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000097:blood; D012964:Sodium / Q000652:urine; D013564:Sympathetic Nervous System / Q000502:physiology*
D012964:Sodium; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine