Orthostatic Responses to Nitric Oxide Synthase Inhibition in Persons With Tetraplegia

Wecht JM, Radulovic M, LaFountaine MF, Rosado-Rivera D, Zhang R-L, Bauman WA. Orthostatic responses to nitric oxide synthase inhibition in persons with tetraplegia. Objectives: To determine the effects of 1.0mg/kg nitro-l-arginine methyl ester (L-NAME) on orthostatic mean arterial pressure (MAP), serum aldosterone, and plasma renin concentrations in persons with chronic tetraplegia compared with nonspinal cord-injured controls. Design: Prospective placebo-controlled intervention study. Setting: James J. Peters Veterans Affairs Medical Center. Participants: Patients (n=5) with tetraplegia and controls (n=7) participated. The groups were matched for age, height, and weight; the average duration of injury in the tetraplegia group was 22±14 years. Intervention: Subjects with tetraplegia visited the laboratory twice, receiving placebo on day 1 and L-NAME (1.0mg/kg) on day 2. The agents were infused via an intravenous catheter over 60 minutes with the patient in the supine position. Data were collected during the infusion and then during head-up tilt to 45° for 30 minutes. Control subjects visited the laboratory once for placebo infusion and the head-up tilt maneuver. Main Outcome Measure: Orthostatic MAP. Results: Orthostatic MAP was reduced after placebo infusion in subjects with tetraplegia compared with controls (69±11 vs 89±9mmHg, respectively; P<.01) and compared with L-NAME infusion (90±16mmHg; P<.01). Orthostatic MAP did not differ when comparing the tetraplegia group with controls after L-NAME infusion. Orthostatic aldosterone levels were increased after placebo compared with L-NAME infusion in persons with tetraplegia; plasma renin levels did not differ among the groups. Conclusions: These data suggest that nitric oxide synthase inhibition may have clinical potential for treatment of orthostatic hypotension in persons with chronic tetraplegia.