Hemodynamic significance of histamine synthesis and histamine H1- and H2-receptor gene expression during endotoxemia

Naunyn Schmiedebergs Arch Pharmacol. 2002 Dec;366(6):513-21. doi: 10.1007/s00210-002-0651-x. Epub 2002 Oct 29.


The hypothesis that endotoxemia may modify histamine synthesis or histamine receptor expression and that these changes may contribute to cardiovascular dysfunction was tested in rabbits which were rendered endotoxemic by lipopolysaccharide (LPS; 100 micro g/kg, i.v.). The plasma histamine concentration was elevated shortly after LPS, remaining elevated (a 50-fold increase) over the experimental period of 6 h. The sustained increase in plasma histamine was associated with a time-dependent increase in expression of histidine decarboxylase (HDC) in different tissues including atrium, as determined by Western blot analysis. The H(1)-receptor antagonist diphenhydramine significantly shortened the duration of the initial hypotension and the H(2)-receptor antagonist ranitidine greatly suppressed the lasting tachycardia following LPS injection. Northern blot analysis showed that LPS dramatically induced gene expressions of histamine H(1)- and H(2)-receptors in cardiac tissues. In right atrium isolated from the septic animal, the positive chronotropic effect of histamine was significantly diminished. This was possibly due to a marked reduction in G(s)(alpha) protein expression, indicating the impaired H(2)-receptor cellular signaling. In conclusion, LPS-induced endotoxemia causes prominent increases in production of histamine through induction of HDC and in gene expression of histamine receptors. We suggest that overproduction of histamine may be partly responsible for the hemodynamic alterations of endotoxemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Endotoxemia / blood
  • Endotoxemia / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Hemodynamics / drug effects
  • Hemodynamics / physiology*
  • Histamine / biosynthesis*
  • Histamine / blood
  • Histamine / pharmacology
  • Male
  • Rabbits
  • Receptors, Histamine H1 / biosynthesis*
  • Receptors, Histamine H1 / genetics


  • Receptors, Histamine H1
  • Histamine