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. Design and 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 μmol/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 μmol/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.

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