The lipopolysaccharide-induced up-regulation of bradykinin B2-receptor in the mouse heart is mediated by tumor necrosis factor-alpha and angiotensin II.
Our present study aimed to characterize the effects of lipopolysaccharide (LPS) on the expression of the bradykinin B2-receptor in the mouse heart, which may have a role in cardiac depression during sepsis. We found that LPS induced the up-regulation of B2-receptor mRNA in the heart in vivo and in cultured cardiac myocytes in vitro. Like LPS, tumor necrosis factor-alpha (TNF-alpha) but not interleukin (IL)-1-beta, IL-6 or endothelin-1 stimulated B2-receptor expression in cultured myocytes. The effect of LPS on the expression of B2-receptor mRNA was also mimicked in cardiac myocytes by Ang II via Ang II type 1 (AT1-) receptor. Losartan, an AT1-receptor antagonist, inhibited about 50% of the LPS-induced up-regulation of B2-receptor mRNA in the heart in vivo and in cultured cardiac myocytes in vitro. Furthermore, the up-regulation of B2-receptor mRNA by either LPS or Ang II in cultured myocytes was abolished by anti-TNF-alpha antibody. These results suggest that the up-regulation of cardiac B2-receptor expression by LPS is mediated through TNF-alpha, which is produced in the myocardium by two different mechanisms in an AT1-receptor-dependent and independent manners, implying the role of the cardiac kallikrein-kinin system in the development of cardiac dysfunction during sepsis.
Yayama
Katsutoshi
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan.
Hiyoshi
Hiromi
H
Sugiyama
Kaori
K
Okamoto
Hiroshi
H
D000804:Angiotensin II / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000276:immunology / Q000378:metabolism*; D032383:Myocytes, Cardiac; D012333:RNA, Messenger / Q000096:biosynthesis; D043782:Receptor, Bradykinin B2 / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D015854:Up-Regulation
D057911:Angiotensin Receptor Antagonists; D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II