PROLONGED NOS INHIBITION IN THE BRAIN ELEVATES BLOOD-PRESSURE IN NORMOTENSIVE RATS

Systemic inhibition of nitric oxide synthase (NOS) evokes hypertension , which is enhanced by salt loading, partly via augmented sympathetic activity. Pie investigated whether inhibition of brain NOS elevates bl ood pressure (BP) in normotensive rats and, if so, whether the BP elev ation is enhanced by salt loading. After a 2-wk low-salt (0.3%) diet, male Sprague-Dawley (SD) rats were divided into four groups. Groups 1 and 2 received a chronic intracerebroventricular infusion of 0.5 mg . kg(-1) . day(-1) of N-G-monomethyl-L-arginine (L-NMMA), and groups 3 a nd 4 were given artificial cerebrospinal fluid (aCSF). Groups 1 and 3 were placed on a high-salt (8%) diet, whereas groups 2 and 4 were on a low-salt diet. On day 9 or 10, group 1 showed significantly higher me an arterial pressure (MAP) in a conscious unrestrained state (129 +/- 3 mmHg vs. 114 +/- 3, 113 +/- 1 and 108 +/- 3 mmHg in groups 2, 3, and 4, respectively, P < 0.05). On a high-salt diet, response of renal sy mpathetic nerve activity but not of BP to air-jet stress was significa ntly larger in rats given L-NMMA than in rats given aCSF (29 +/- 4% vs . 19 +/- 3%, P < 0.05). When the intracerebroventricular infusions wer e continued for 3 wk, MAP was significantly higher in rats given L-NMM A than in rats given aCSF irrespective of salt intake, although the di fference was similar to 7 mmHg. Thus chronic inhibition of NOS in the brain only slightly elevates BP in SD rats. Salt loading causes a more rapid rise in BP The mechanisms of the BP elevation and its accelerat ion by salt loading remain to be elucidated.