Submitted on March 22, 2007
Accepted on October 21, 2007
DIRECT AND REFLEXIVE EFFECTS OF NITRIC OXIDE SYNTHASE INHIBITION ON BLOOD PRESSURE
Jill M Wecht1*, Joseph P Weir2, David S Goldstein3, AnnMarie H Krothe-Petroff4, Ann M Spungen5, Courtney Holmes3, and William A Bauman1
1 Rehabilitation Medicine, Mount Sinai School of Medicine, New York, New York, United States; Medicine, Mount Sinai School of Medicine, New York, New York, United States; Center of Excellence for the Medical Consequences of SCI, James J. Peters VA Medical Center, Bronx, New York, United States
2 Des Moines University-Osteopathic Medical Center, Des Moines , Iowa, United States
3 Clinical Neurocardiology Section, CNP, DIR, NINDS, National Institutes of Health, Bethesda , Maryland, United States
4 Center of Excellence for the Medical Consequences of SCI, James J. Peters VA Medical Center, Bronx, New York, United States
5 Center of Excellence for the Medical Consequences of SCI, James J. Peters VA Medical Center, Bronx, New York, United States; Rehabilitation Medicine, Mount Sinai School of Medicine, New York, New York, United States; Medicine, Mount Sinai School of Medicine, New York, New York, United States
* To whom correspondence should be addressed. E-mail: jm.wecht{at}va.gov.
Direct effects of vasoactive substances on blood pressure can be examined in persons with tetraplegia due to disruption of descending spinal pathways to sympathetic pre-ganglionic neurons, as cervical lesions interfere with baroreceptor reflex buffering of sympathetic outflow. In this study, we assessed effects of the nitric oxide synthase (NOS) inhibitor, nitro-L-arginine methyl ester (L-NAME), on mean arterial pressure (MAP), heart rate (HR), and plasma norepinephrine (NE) concentrations in persons with tetraplegia compared to a neurologically-intact control group. Seven individuals with tetraplegia and 7 age matched controls received, on separate visits and in the following order, placebo (30 ml normal saline) and 0.5, 1, 2, and 4 mg/kg L-NAME intravenously over 60 minutes. Supine hemodynamic data were collected and blood was sampled at the end of each infusion and at 120, 180, and 240 minutes thereafter. L-NAME increased MAP, and the relative increase was greater in the tetraplegia group than in the control group. HR was reduced following L-NAME administration in both groups. L-NAME decreased plasma NE in the control group but not in the group with tetraplegia. These findings suggest that reflexive sympathoinhibition normally buffers the pressor response to NOS inhibition, an effect which is not evident in persons with tetraplegia due decentralized sympathetic vasomotor control.
