Nitric oxide has been implicated in the regulation of cardiac contract
ile function as well as the depressed myocardial contractility associa
ted with sepsis and endotoxemia We examined the effects of nitric oxid
e synthase (NOS) inhibitors and a nitric oxide generator on contractil
e responses of left atrial preparations and ventricular myocytes isola
ted from endotoxemic guinea pigs, which exhibit depressed myocardial c
ontractile function. The NOS inhibitor L-NAME had no effect on contrac
tile tension developed by control atria or atria isolated from guinea
pigs 4 or 16 h after an intraperitoneal injection of endotoxin. Simila
rly, contraction of ventricular myocytes isolated from control or endo
toxemic guinea pigs (4 h after endotoxin injection) was unchanged by e
xposure to several NOS inhibitors. In addition, neither Ca2+-dependent
nor Ca2+-independent ventricular NOS activity was affected by endotox
emia. These data suggest that nitric oxide alone is not responsible fo
r the cardiac contractile dysfunction of endotoxemic guinea pigs.