Centrally produced neuronal nitric oxide in the control of baroreceptor reflex sensitivity and blood pressure in normotensive and spontaneously hypertensive rats

We studied the effect of chronic nitric oxide synthase (NOS) blockade in th e brain on mean arterial pressure [MAP (mmHg)], heart rate [HR (bpm)] and b aroreceptor reflex sensitivity [BRS (mean slope: bpm/mmHg)] in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Intracerebroventricular ( i.c.v.) infusion of the nonselective NOS inhibitor N-Nitro-L-arginine-methy lester (L-NAME) (50 mu g/kg per day, 11-12 days) increased MAP in WKY and S HR (125 +/- 2.1 vs 118 +/- 1.1 controls, P<0.01 and 179+/-3.59 vs 156+/-4.0 controls, P<0.001, respectively) without affecting HR. In L-NAME-treated W KY, BRS to bradycardia was suppressed (-0.79+/-0.09 vs -1.76+/-0.17 control s, P=0.001), whereas in SHR, L-NAME did not affect BRS to bradycardia. BRS to tachycardia remained unaffected in either strain. In WKY, 7-nitroindazol e (7-NI . Na+) (34 mu g i.c.v./kg per day, 11-12 days), a selective nNOS in hibitor, did not affect MAP or HR, but BRS to bradycardia and tachycardia w as decreased (-0.37+/-0.20 vs -0.97+/-0.41 controls, P<0.01 and -1.78+/-0.2 0 vs 2.52+/-0.40 controls, P=0.05, respectively). In SHR, the same dose of 7-NI . Na+ increased resting MAP (171+/-5.00 vs 150+/-7.00 controls, P<0.05 ) without affecting HR or BRS to bradycardia or tachycardia. Thus in WKY, B RS to acute changes in systemic blood pressure (BP) is regulated by NO prod uced by nNOS in the brain, serving asa neurotransmitter in sympathetic and parasympathetic efferent pathways. In SHR, systemic BP is regulated in part by NO released by the type I NOS isoenzyme in the brain.