Nitric oxide inhalation and nitric oxide synthase inhibitor supplement for endotoxin-induced hypotension

BACKGROUND: This study was performed to determine whether a combined therapy of nitric oxide (NO) inhalation and nitric oxide synthase (NOS) inhibitor is effective in experimental animals with endotoxin-induced refractive hypotension accompanied by pulmonary hypertension. METHODS: Escherichia coli lipopolysaccharide (1 mg/kg) was administered to 10 newborn piglets to induce endotoxemia. The experiment then began 60 min later, when the systemic arterial pressure dropped. The inhalation of 20 p.p.m. NO at 60 and 120 min of endotoxemia created a control group. Another group was also administered N w-nitro-L-arginine (L-NNA; 5 mg) after the first NO inhalation at 60 min of endotoxemia (the L-NNA group). Pulmonary arterial pressure, systemic arterial pressure and cardiac output were measured and compared among the groups. RESULTS: Three of the 5 piglets in the control group died of hypotensive shock, while in the L-NNA group the systemic arterial pressure recovered to pre-endotoxin administration levels. The L-NNA group produced a further increase in pulmonary arterial pressure against which NO inhalation was effective. CONCLUSION: Nitric oxide inhalation alone carries a potential risk of further lowering systemic arterial pressure in a piglet with hypotension induced by endotoxin, whereas the combined therapy resulted in the recovery of the blood pressure to pre-endotoxin levels. The combined therapy was simultaneously effective against pulmonary hypertension.