Orthostatic effects of midodrine versus L-NAME on cerebral blood flow and the renin-angiotensin-aldosterone system in tetraplegia

Objective: To compare responses to head-up tilt (HUT) in individuals with chronic tetraplegia after midodrine hydrochloride (10mg) versus nitro-L-arginine methyl ester (L-NAME, 1mg/kg) administration. Design: Prospective comparative drug trial. Setting: Veterans Affairs medical center. Participants: Participants (N=7) were studied during 3 laboratory visits: no drug, midodrine (administered orally 30min before HUT), and L-NAME (infused over a 60-min period). Interventions: Anti-hypotensive agents, midodrine, and L-NAME. Main Outcome Measures: Mean arterial pressure (MAP), cerebral blood flow (CBF), and markers of the renin-angiotensin-aldosterone system (RAAS, plasma renin and serum aldosterone) were measured in the supine position at baseline (BL) and during a 45° HUT maneuver. Data were compared between BL and the average of 3 assessments collected during HUT. Results: Orthostatic MAP and CBF were increased with the midodrine and L-NAME groups compared with the no drug trial and the relationship between the change in MAP and CBF was significant (r=0.770; P<0.001). Both L-NAME and midodrine appeared to suppress the post-HUT RAAS response compared with no drug. Conclusions: Increasing orthostatic blood pressure with L-NAME or midodrine appears to increase CBF and suppress the RAAS during HUT in persons with tetraplegia, although more data are needed to confirm these preliminary findings.