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

摘要: The hypothesis that endotoxemia may modify histamine synthesis or receptor expression and these changes contribute to cardiovascular dysfunction was tested in rabbits which were rendered endotoxemic by lipopolysaccharide (LPS; 100 µg/kg, i.v.). plasma concentration elevated shortly after LPS, remaining (a 50-fold increase) over the experimental period of 6 h. sustained increase associated with a time-dependent histidine decarboxylase (HDC) different tissues including atrium, as determined Western blot analysis. H1-receptor antagonist diphenhydramine significantly shortened duration initial hypotension H2-receptor ranitidine greatly suppressed lasting tachycardia following LPS injection. Northern analysis showed dramatically induced gene expressions H1- H2-receptors cardiac tissues. In right atrium isolated from septic animal, positive chronotropic effect diminished. This possibly due marked reduction Gsα protein expression, indicating impaired cellular signaling. conclusion, LPS-induced causes prominent increases production through induction HDC receptors. We suggest overproduction be partly responsible for hemodynamic alterations endotoxemia.