Neuronal nitric oxide strongly suppresses sympathetic outflow in high-salt Dahl rats.
OBJECTIVE
To investigate the effects of a selective inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitroindazole, on peripheral sympathetic outflow in Dahl rats.


METHODS
Dahl salt-sensitive and salt-resistant rats were fed either a regular-salt (0.4% NaCl) or a high-salt (8% NaCl) diet for 4 weeks. In chronically instrumented conscious rats, renal sympathetic nerve activity (RSNA) was measured in both baroreceptor-loaded and baroreceptor-unloaded states. The baroreceptor unload was performed by decreasing arterial pressure with occlusion of the inferior vena cava.


RESULTS
7-Nitroindazole (307 micromol/kg intraperitoneally) increased resting RSNA from 24 +/- 3% to 38 +/- 6% with an increase in mean arterial pressure of 15 +/- 3 mmHg, and increased baroreceptor-unloaded RSNA from 100% to 278 +/- 16% in salt-sensitive Dahl rats receiving a high-salt diet However, 7-nitroindazole did not increase resting RSNA, but did increase baroreceptor-unloaded RSNA from 100% to 179 +/- 15%, 177 +/- 15%, and 133 +/- 4% in salt-sensitive Dahl rats receiving a regular-salt diet, salt-resistant Dahl rats receiving a high-salt diet, and salt-resistant Dahl rats receiving a regular-salt diet, respectively. The high-salt diet significantly increased the baroreceptor-unloaded RSNA more than the regular-salt diet did, in both salt-sensitive and salt-resistant rats. After administration of the vehicle for 7-nitroindazole (peanut oil), L-arginine (100 micromol/kg per min for 10 min) decreased both resting and baroreceptor-unloaded RSNA, whereas after pretreatment with 7-nitroindazole, the L-arginine-induced suppression was reversed, in Dahl salt-sensitive rats receiving a high-salt diet.


CONCLUSIONS
Neuronal nitric oxide may suppress the sympathetic discharge generated before baroreflex-mediated inhibition in all rats. This neuronal nitric oxide-mediated suppression was enhanced by the salt load in both salt-resistant and salt-sensitive Dahl rats. Finally, the neuronal nitric oxide-mediated suppression in tonic peripheral sympathetic outflow may be greatly enhanced in salt-sensitive hypertension.
Nishida
Y
Y
Second Department of Physiology, National Defense Medical College, Tokorozawa, Saitama, Japan. ynishida@cc.ndmc.ac.jp
Chen
Q H
QH
Tandai-Hiruma
M
M
Terada
S
S
Horiuchi
J
J
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D020303:Rats, Inbred Dahl / Q000502:physiology*; D012146:Rest; D012965:Sodium Chloride / Q000008:administration & dosage* / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D007191:Indazoles; D009569:Nitric Oxide; D012965:Sodium Chloride; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C080122:7-nitroindazole