Neuronal nitric oxide strongly suppresses sympathetic outflow in high-saltDahl rats

Objective To investigate the effects of a selective inhibitor of neuronal n itric oxide synthase (nNOS), 7-nitroindazole, on peripheral sympathetic out flow in Dahl rats. Design and methods Dahl salt-sensitive and salt-resistant rats were fed eit her a regular-salt (0.4% NaCl) or a high-salt (8% NaCl) diet for 4 weeks. I n 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 pressu re with occlusion of the inferior vena cava, Results 7-Nitroindazole (307 mu mol/kg intraperitoneally) increased resting RSNA from 24 +/- 3% to 38 +/- 6% with an increase in mean arterial pressur e of 15 +/- 3 mmHg, and increased baroreceptor-unloaded RSNA from 100% to 2 78 +/- 16% in salt-sensitive Dahl rats receiving a high-salt diet. However, 7-nitroindazole did not increase resting RSNA, but did increase barorecept or-unloaded RSNA from 100% to 179 +/- 15%, 177 +/- 15%, and 133 +/- 4% in s alt-sensitive Dahl rats receiving a regular-salt diet, salt-resistant Dahl rats receiving a high-salt diet, and salt-resistant Dahl rats receiving a r egular-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 vehicl e for 7-nitroindazole (peanut oil), L-arginine (100 mu mol/kg per min for 1 0 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 ge nerated before baroreflex-mediated inhibition in all rats. This neuronal ni tric 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.