Normalization of supine blood pressure after nitric oxide synthase inhibition in persons with tetraplegia.
OBJECTIVE
Orthostatic hypotension is a well-defined clinical consequence of spinal cord injury (SCI), particularly in those with tetraplegia. The etiology of orthostatic hypotension is thought to be loss of sympathetic vasomotor control, although other factors may play a role. There is evidence of up-regulation of nitric oxide synthase (NOS) activity after hind-limb suspension in rats, a condition of antigravity that may have similar vascular effects as shown in persons with tetraplegia caused by paralysis. The study objective was to determine the effect of a NOS inhibitor (nitro-L-arginine methyl ester [L-NAME]) on supine mean arterial pressure in persons with chronic tetraplegia compared with non-SCI controls.


METHODS
Fourteen individuals participated (7 with tetraplegia and 7 controls). Subjects visited the laboratory twice for placebo on day 1 and L-NAME (1 mg/kg) on day 2; both were infused intravenously over 60 minutes. Blood pressure was monitored for 3 hours after infusion at the brachial artery using a standard manual cuff.


RESULTS
Mean arterial pressure (MAP) was lower at baseline (P < 0.05) and after placebo administration (P < 0.0001) in the tetraplegia group compared with the control group. L-NAME increased MAP in both groups; however, the relative increase was greater in the tetraplegia group compared with the control group, such that group differences for MAP were eliminated. Supine MAP was normalized with L-NAME, and there was an increased sensitivity to NOS inhibition in the group with tetraplegia.


CONCLUSIONS
These findings indicate that blood pressure dysregulation in persons with tetraplegia may reflect increased vascular NO and suggest a novel treatment of hypotension using NOS inhibition in this population.
Wecht
Jill M
JM
VA Center of Excellence, James J. Peters VA Medical Center, Bronx, New York 10468, USA. jwecht@hotmail.com
Weir
Joseph P
JP
Krothe
AnnMarie H
AH
Spungen
Ann M
AM
Bauman
William A
WA
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D004562:Electrocardiography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011782:Quadriplegia / Q000188:drug therapy*; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D016683:Supine Position
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester