Lipopolysaccharide induces apoptosis in adult rat ventricular myocytes via cardiac AT1 receptors

Lipopolysaccharide (LPS) from gram-negative bacteria circulates in acute, subacute, and chronic conditions. It was hypothesized that LPS directly induces cardiac apoptosis. In adult rat ventricular myocytes (isolated with depyrogenated digestive enzymes to minimize tolerance), LPS (10 ng/ml) decreas...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2002-08, Vol.52 (2), p.H461-H467
Main Authors: HAI LING LI, SUZUKI, Jun, BAYNA, Evelyn, ZHANG, Fu-Min, DALLE MOLLE, Erminia, CLARK, Aaron, ENGLER, Robert L, LEW, Wilbur Y. W
Format: Article
Language:English
Subjects:
Bacterial diseases
Biological and medical sciences
Cardiology
Cellular biology
Circulatory system
Experimental bacterial diseases and models
Heart
Infectious diseases
Medical sciences
Rodents
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Summary:Lipopolysaccharide (LPS) from gram-negative bacteria circulates in acute, subacute, and chronic conditions. It was hypothesized that LPS directly induces cardiac apoptosis. In adult rat ventricular myocytes (isolated with depyrogenated digestive enzymes to minimize tolerance), LPS (10 ng/ml) decreased the ratio of Bcl-2 to Bax at 12 hours; increased caspase-3 activity at 16 hours; and increased annexin V, propidium iodide, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining at 24 hours. Apoptosis was blocked by the caspase inhibitor benzyloxycarbonyl-valine-alanine-aspartate fluoromethylketone (Z-VAD-fmk), captopril, and angiotensin II type 1 receptor (AT1) inhibitor (losartan), but not by inhibitors of AT2 receptors (PD-123319), tumor necrosis factor- (TNFRII:Fc), or nitric oxide (NG-monomethyl-L-arginine). Angiotensin II (100 nmol/l) induced apoptosis similar to LPS without additive effects. LPS in vivo (1 mg/kg iv) increased apoptosis in left ventricular myocytes for 1-3 days, which dissipated after 1-2 wk. Losartan (23 mg kg1 day1 in drinking water for 3 days) blocked LPS-induced in vivo apoptosis. In conclusion, low levels of LPS induce cardiac apoptosis in vitro and in vivo by activating AT1 receptors in myocytes.
ISSN:0363-6135
1522-1539