Effect of H1 and H2 receptor blockers on mobilization of myocardial carnosine to histamine during compound 48/80-induced shock in young rats.
Histamine exerts profound effects on the cardiovascular system during shock mediated by H1 and H2 receptors. The source of histamine is uncertain. It is our hypothesis that carnosine serves as a nonmast-cell reservoir for histidine, utilized for histamine synthesis during shock. We have shown that treatment of older rats with compound 48/80, a mast cell degranulator, produces age-dependent lethal stress, which is prevented by lodoxamide (LOD), a mast cell degranulation inhibitor, is exacerbated by H2 receptor blockade, and is accompanied by increased mobilization of myocardial carnosine to histidine and histamine. This study was designed to evaluate the effects of H1 and H2 blockers on carnosine mobilization to histamine during 48/80-induced shock in young rats. Fifty male SD rats (125 g) were divided into nine groups: saline; LOD; H1 blocker diphenhydramine (DPH); H2 blocker cimetidine (CIM); 48/80; LOD + 48/80; DPH + 48/80; CIM + 48/80; and DPH + CIM + 48/80. All rats were sacrificed 30 min after final injections and hearts were analyzed via HPLC. There was a reduction in myocardial carnosine (P less than or equal to 0.01) and histidine (P less than or equal to 0.001) and a simultaneous increase in histamine (P less than or equal to 0.01, P less than or equal to 0.001) in animals receiving 48/80 or CIM + 48/80, respectively, compared to controls or groups pretreated with LOD, DPH, or DPH + CIM. These results indicate that 48/80-induced shock increases mobilization of myocardial carnosine and histidine to histamine, which supports a role for carnosine as a nonmast-cell histamine source.(ABSTRACT TRUNCATED AT 250 WORDS)
Fitzpatrick
J C
JC
Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick.
Fisher
H
H
Flancbaum
L
L
D000818:Animals; D002336:Carnosine / Q000378:metabolism*; D015550:Cell Degranulation / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology; D004151:Dipeptides / Q000378:metabolism*; D004155:Diphenhydramine / Q000494:pharmacology; D004347:Drug Interactions; D006632:Histamine / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012769:Shock / Q000139:chemically induced / Q000378:metabolism*; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity*
D004151:Dipeptides; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D003189:p-Methoxy-N-methylphenethylamine; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine; D002336:Carnosine; D010072:Oxamic Acid; C021702:lodoxamide ethyl