Nitric oxide scavenging modulates an experimental vasoplesia in-vitro

Endogenous overproduction of nitric oxide (NO) is believed to be a primary cause of refractory hypotension in septic shock. Under this condition, effectiveness of vasopressors is diminished due to hyporeactivity of blood vessels, a condition termed as vasoplesia. Effective reduction of NO levels should alleviate the condition. In this study, we investigated whether NO scavenging could modulate the endotoxin mediated vasoplesia in-vitro. Further, we explored whether NO scavenging in combination with a moderate NO synthase (NOS) inhibition would also be effective in modulating NO mediated vasoplesia. Experimental vasoplesia was produced in-vitro by incubating isolated rat thoracic aortic rings with lipopolysaccharide (LPS). Vessel rings were then treated with N(omega)-nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor), human hemoglobin (Hb; a NO scavenger), or both L-NAME and Hb. Vascular reactivity was assessed by measuring vessel ring isometric tension changes to norepinephrine (NE) doses; the median effective doses (logEC50) of NE before and after each experimental treatment were compared. Following a 6-hour LPS treatment, vascular reactivity logEC50 values for NE were significantly increased compared with control vessel rings incubated without LPS. Treatment with either L-NAME alone or Hb alone significantly improved the vessel ring reactivity to NE. When both L-NAME and Hb were used concomitantly, vascular reactivity was also significantly improved. These results indicate that NO scavenging with Hb is as effective as NO synthesis inhibition with NAME in modulating the endotoxin induced vasoplesia. In conclusion, NO scavenging, alone or in combination with a moderate NOS inhibition, may render an alternative therapeutic approach to NOS synthesis inhibition in modulating the vasoplesia in septic shock.