Rapid increase in inducible nitric oxide synthase gene expression in the heart during endotoxemia

Inducible, Ca(2+)-independent nitric oxide (NO) synthase activity in the heart is elevated during endotoxemia and the resulting excess release of NO depresses cardiac contractile function. We show here that this is due to an extremely rapid induction of inducible NO synthase gene expression. Following injection of endotoxin (bacterial lipopolysaccharide) in rats we detected increased inducible NO synthase mRNA levels in the left ventricular wall within 30 min which then peaked at 3 h. This was followed by an increase in myocardial inducible NO synthase enzyme activity and plasma levels of NO metabolites, nitrate and nitrite, which peaked at 6 and 12 h, respectively. The extremely rapid induction of inducible NO synthase may serve to protect the heart against microbial infection and concomitantly alter myocardial mechanical function.