Endotoxin induces cardiac HSP70 and resistance to endotoxemic myocardial depression in rats.
Endotoxin (bacterial lipopolysaccharide, LPS) depresses myocardial function. However, heat shock and sublethal LPS can confer cardiac resistance to postischemic dysfunction. We hypothesized that a prior exposure to LPS stress induces the expression of cardiac heat shock protein 70 (HSP70) and resistance to endotoxemic myocardial depression. Moreover, induction of HSP70 by hyperthermia should also increase cardiac resistance to LPS toxicity. LPS (500 micrograms/kg ip) depressed rat left ventricular developed pressure (LVDP) maximally at 6 h (58.4 +/- 3.72 vs. 101 +/- 1.46 mmHg in saline control, P < 0.01), and myocardial contractile function recovered at 24 h. In rats pretreated with LPS 24 h earlier, subsequent LPS exposure did not depress LVDP (97.0 +/- 3.53 mmHg at 6 h, P < 0.01 vs. single exposure). Both LPS and hyperthermia (42 degrees C, 15 min) induced HSP72 mainly in the cardiac interstitial cells, including macrophages at 24 h after treatment. When hyperthermia-pretreated animals were similarly challenged with LPS, myocardial depression at 6 h was partially abrogated (LVDP 80.1 +/- 5.67 vs. 62.2 +/- 4.91 mmHg in sham+LPS group, P < 0.01). We conclude that LPS induces HSP70 in rat heart and that an exposure to LPS or heat stress confers cardiac resistance to endotoxemic myocardial depression.
Meng
X
X
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
Brown
J M
JM
Ao
L
L
Nordeen
S K
SK
Franklin
W
W
Harken
A H
AH
Banerjee
A
A
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006321:Heart / Q000187:drug effects; D018869:Heat-Shock Response / Q000187:drug effects*; D007668:Kidney / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides; D009124:Muscle Proteins; D012333:RNA, Messenger