Elevated
nitric oxide (NO) levels appear to be a primary cause of the
sepsis related
hypotension. We tested a hypothesis that a concomitant NO synthesis inhibition (NOSI) and NO scavenging (NOSC) could effectively modulate this
hypotension. Anesthetized SD rats were subjected to endotoxemic
shock by
intravenous administration of
endotoxin (LPS; 10mg/kg). Three hours post-LPS, the animals were randomly divided into three groups and infused with 25mg/kg of N-amino-L-methyl
ester (NAME; a NO synthesis inhibitor, N = 4), 130 mg/kg human
hemoglobin (Hb; a NO scavenger, N = 6), or a mixture of both (130mgHb/kg and 25mg NAME/kg, N = 4). Changes in mean blood pressure (MBP) and erythrocyte and plasma nitrosyl Hb (
HbNO) levels were followed. The initial MBP increase of the combined treatment was significantly greater than Hb or NAME alone (P < 0.05, t-test) and was maintained significantly above the pre-treatment values (P < 0.05, paired t-test) 2hrs
after treatment. All post-LPS erythrocyte samples exhibited the characteristic electron spin resonance signals of
HbNO at 3.4 kGauss indicating NO formation in
endotoxemia. The
HbNO signal was also detected in plasma of rats treated with Hb alone or with Hb and NAME indicating the infused Hb reacted with NO. These results indicate that concomitant NOSI and NOSC is more effective than NOSI or NOSC alone in modulating the
hypotension of
sepsis as it combines two distinct but mutually complementary anti-NO mechanisms.