Acute stress induces cardiac mast cell activation and histamine release, effects that are increased in Apolipoprotein E knockout mice

Objectives: Cardiac mast cells have recently been found to be activated in atherosclerotic coronary arteries. but no mediator has so far been documented to be released front them nor have they been investigated in Apolipoprotein (Apo) E knockout (k/o) mice that develop atherosclerosis. Psychological stress triggers acute coronary syndrome, while acute restraint stress stimulates rat cardiac mast cells, the main mediator of which histamine is a coronary constrictor. Here. we investigated the effect of acute stress on the activation of cardiac mast cells morphologically, as well as the levels of cardiac and serum histamine in normal and genetically deficient mice. Methods: Male. 8-14 week-old ApoE k/o mice and their corresponding control C57BL/6J mice were used. significant reduction of cardiac histamine from 396.7 +/- 45.6 to 214.6 +/- 41.5 ng/g was observed over 120 min restraint stress with a corresponding increase in serum histamine from 126.9 +/- 4.0 to 188.4 +/- 17.3 ng/ml in C57BL mice. Cardiac mast cell activation was observed by light and electron microscopy. Both basal cardiac and serum histamine in ApoE k/o mice was significantly higher than that in C57BL mice. Although the extent of mast cell activation in ApoE k/o mice was similar to that of C57BL mice, the number of cardiac mast cells in ApoE k/o mice was 37% higher. Histamine levels were hardly detectable with or without stress in W/W-v mast cell deficient mice. Conclusions: Acute restraint stress triggered cardiac histamine release in mice that was clearly derived front mast cells, as it was absent in W/W-v mice. The high basal cardiac and serum histamine in ApoE k/o mice. along with the high number of cardiac mast mells, suggest possible ongoing cardiac mast cell activation that may participate in atherosclerosis. These results may possibly help understand stress-related cardiovascular pathology. (C) 2002 Elsevier Science B.V All rights reserved.