Fatimunnisa Qadri1,2,*, Oscar A. Carretero1 and
A. Guillermo Scicli1,#
1Hypertension and Vascular Research Division, Henry Ford Hospital,
Detroit, MI 48202 - 2689, USA
2Institute for Experimental and Clinical Pharmacology and Toxicology,
Medical University of Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany
(*) To whom correspondence should be addressed(2).
# Present address: Eye Care Services Research, Henry Ford Health
Systems, 1 Ford Place, 4D, Detroit, MI 48202 - 3450, USA
Abstract: We studied the effect of chronic nitric oxide synthase
(NOS) blockade in the brain on mean arterial pressure [MAP (mmHg)], heart
rate [HR (bpm)] and baroreceptor 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-methylester
(LNAME) (50 μg/kg per day, 11 - 12 days) increased MAP in WKY and SHR (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 WKY, BRS to bradycardia
was suppressed (-0.79±0.09 vs -1.76±0.17 controls, 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-nitroindazole (7-NI・Na+)
(34 μg i.c.v./kg per day, 11 - 12 days), a selective nNOS inhibitor, did
not affect MAP or HR, but BRS to bradycardia and tachycardia was decreased
(-0.37±0.20 vs -0.97±0.41 controls, P<0.01 and -1.78±0.20 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, BRS to acute
changes in systemic blood pressure (BP) is regulated by NO produced by nNOS
in the brain, serving as a 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.
Keywords: Brain nitric oxide, Baroreceptor reflex sensitivity, Wistar-Kyoto
rat,
Spontaneously hypertensive rat, Nitric oxide synthase activity