Nitric oxide production within cardiac myocytes reduces their contractility in endotoxemia.
We investigated whether increased nitric oxide (NO) synthase activity within cardiac myocytes contributes to the depressed cardiac contractility observed in endotoxic shock. Isolated ventricular myocytes were studied to examine the effects of substrates and inhibitors of NO synthase on myocyte contractility. When stimulated electrically, the resting length of myocytes from control animals shortened by 5.3 +/- 0.3% (means +/- SE, n = 32). Baseline contraction of myocytes from endotoxin-treated animals was reduced to 3.0 +/- 0.3% (n = 17, P < 0.001). The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) had no effect on myocytes from control animals, but it increased the contraction of myocytes from endotoxin-treated animals by 40% (fractional shortening increased to 4.3 +/- 0.4%, P < 0.01). Similar results were obtained with NG-methyl-L-arginine. The effect of L-NAME could be reversed by excess L-arginine, but not D-arginine. The effect of endotoxin was abolished by dexamethasone pretreatment. Methylene blue also reversed the effects of endotoxin but had toxic effects on myocytes. Agents that either prevent synthesis or the effects of NO reverse the depression of myocyte contraction seen following endotoxin treatment.
Brady
A J
AJ
Department of Cardiac Medicine, National Heart and Lung Institute, London, United Kingdom.
Poole-Wilson
P A
PA
Harding
S E
SE
Warren
J B
JB
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D006168:Guinea Pigs; D008751:Methylene Blue / Q000494:pharmacology; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004731:Endotoxins; D009569:Nitric Oxide; D003907:Dexamethasone; D001120:Arginine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester