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Increased resistance to LPS-induced myocardial dysfunction in the Brown Norway rats versus Dahl S rats: roles of inflammatory cytokines and nuclear factor kappaB pathway. Shock 2010 Mar;33(3):332-6



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Scopus ID

2-s2.0-77149177056   13 Citations


We previously demonstrated that hearts from Brown Norway (BN) rats were more resistant to ischemic injury than hearts from Dahl S (SS) rats. Here we determined the susceptibility to LPS-induced cardiomyopathy in these rats and examined the involvement of inflammatory signaling. Both strains were treated with LPS (20 mg/kg) via i.p. injection for 6 h. Myocardial function was assessed by the Langendorff system, and proinflammatory cytokines were measured by the enzyme-linked immunosorbent assay. LPS significantly reduced left ventricular developed pressure in both strains. Interestingly, the decrease of left ventricular developed pressure in BN rat hearts was approximately 25% less than that in SS rat hearts. Furthermore, LPS significantly reduced the peak rate of contraction and the peak rate of relaxation in SS hearts but not in BN hearts. No differences in LPS-induced decreases in coronary flow rate were observed between BN and SS rats. In addition, LPS-induced increases in proinflammatory cytokines, TNF-alpha, IL-1beta, and IL-6, were significantly lower in both plasma and hearts of BN rats compared with production in SS rats. LPS notably up-regulated the expression of proinflammatory enzymes, iNOS and cyclooxygenase 2, in SS hearts but not in BN hearts. Interestingly, LPS did not stimulate Toll-like receptor 4 or its adaptor myeloid differentiation factor 88 expression in the hearts of either strain but did increase IkappaB and P65 phosphorylation, less prominently in BN hearts than in SS hearts. These data indicate that reduced production of proinflammatory cytokines and diminished nuclear factor kappaB activation are major mechanisms by which BN hearts are more resistant to LPS-induced myocardial dysfunction than SS hearts.

Author List

Du J, An J, Wei N, Guan T, Pritchard KA Jr, Shi Y


Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cyclooxygenase 2
Myocardial Contraction
NF-kappa B
Nitric Oxide Synthase Type II
Rats, Inbred BN
Rats, Inbred Dahl
Tumor Necrosis Factor-alpha
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a