LIPOPOLYSACCHARIDE INDUCES CELL SHRINKAGE IN RABBIT VENTRICULAR CARDIAC MYOCYTES

The effects of 10 ng/ml of lipopolysaccharide (LPS) on cell volume wer e examined in rabbit left ventricular myocytes. The myocytes were isol ated with depyrogenated digestive enzymes (<0.7 ng/ml of LPS) to minim ize 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 w ith 1.00 +/- 0.01 in 13 control myocytes (P = 0.0015). LPS-induced cel l shrinkage was completely blocked by coincubation with 1 mM N-monomet hyl-L-arginine, indicating a nitric oxide-mediated mechanism. Cardiac guanosine 3',5'-cyclic monophosphate (cGMP) did not change after Ih bu t increased 6 h after LPS (548 +/- 31 vs. 312 +/- 20 fmol/mg protein i n control cells; P < 0.05). After 8 h, bumetanide (10 mu M for 30 min) , a Na+/K+/2Cl(-) cotransport inhibitor, decreased the CSA in 15 contr ol myocytes to 0.92 +/- 0.02 of the baseline CSA. However, in 19 myocy tes with a CSA of 0.93 +/- 0.01 of baseline after 8 h of LPS, the addi tion of bumetanide caused no additional cell shrinkage. We conclude th at low levels of LPS increase cardiac cGMP to inhibit Na+/K+/2Cl(-) co transport, causing significant cell shrinkage in cardiac myocytes.