Normalization of supine blood pressure after nitric oxide synthase inhibition in persons with tetraplegia

Abstract

Background/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.

Figure 1. Effect of placebo (a) and L-NAME (b) on heart rate in the tetraplegia (squares) and non-SCI (triangles) groups. There was no significant change in HR after placebo or L-NAME administration over the duration of observation in either group.

Figure 2. Effect of placebo (a) and L-NAME (b) on MAP in the tetraplegia (squares) and non-SCI (triangles) groups. MAP was significantly reduced in the tetraplegia group compared with the non-SCI group during the placebo trial (a: P < 0.0001). After L-NAME administration, there was no group difference for MAP over the duration of observation (b). Non-SCI group: *P < 0.05 vs baseline MAP. Tetraplegia group: ^δP < 0.01 and ^ΦP < 0.001 vs baseline MAP.

Figure 3. Percent change in MAP after L-NAME (1 mg/kg) infusion. The increase in hourly MAP (%) was significantly greater in the tetraplegia group compared with the non-SCI group each hour after infusion. *P < 0.05 vs the non-SCI group.