Lipopolysaccharide induces cell shrinkage in rabbit ventricular cardiac myocytes.
The effects of 10 ng/ml of lipopolysaccharide (LPS) on cell volume were examined in rabbit left ventricular myocytes. The myocytes were isolated with depyrogenated digestive enzymes (< 0.7 ng/ml of LPS) to minimize tolerance. Myocyte cross-sectional area (CSA) did not change after 1 h of LPS. However after 8 h, the CSA decreased to 0.93 +/- 0.01 (SE) of the baseline CSA (time = 0) in 19 LPS-exposed myocytes compared with 1.00 +/- 0.01 in 13 control myocytes (P = 0.0015). LPS-induced cell shrinkage was completely blocked by coincubation with 1 mM N-monomethyl-L-arginine, indicating a nitric oxide-mediated mechanism. Cardiac guanosine 3',5'-cyclic monophosphate (cGMP) did not change after 1 h but increased 6 h after LPS (548 +/- 31 vs. 312 +/- 20 fmol/mg protein in control cells; P < 0.05). After 8 h, bumetanide (10 microM for 30 min), a Na+/K+/2Cl- cotransport inhibitor, decreased the CSA in 15 control myocytes to 0.92 +/- 0.02 of the baseline CSA. However, in 19 myocytes with a CSA of 0.93 +/- 0.01 of baseline after 8 h of LPS, the addition of bumetanide caused no additional cell shrinkage. We conclude that low levels of LPS increase cardiac cGMP to inhibit Na+/K+/2Cl- cotransport, causing significant cell shrinkage in cardiac myocytes.
Lew
W Y
WY
Department of Medicine, Department of Veterans Affairs Medical Center, San Diego, California, USA.
Ryan
J
J
Yasuda
S
S
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits; D028021:Sodium-Potassium-Chloride Symporters; D019323:omega-N-Methylarginine / Q000494:pharmacology
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D028021:Sodium-Potassium-Chloride Symporters; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP