Histamine-induced changes in coronary circulation and myocardial oxygen consumption: influences of histamine receptor antagonists.
The effects of histamine and selected H1 and H2 histamine receptor antagonists on cardiac inotropic and chronotropic activity, coronary perfusate flow (CPF), and myocardial oxygen consumption (MVO2) were studied in isolated guinea pig hearts perfused at constant pressure. Data were collected at the end of a 3-min infusion period at steady state. Cardiac performance increased significantly whereas CPF decreased during histamine infusion. MVO2 remained constant owing to a significant increase in myocardial oxygen extraction. Diphenhydramine attenuated the coronary vasoconstriction but potentiated the positive inotropic response. Cimetidine attenuated the inotropic and chronotropic responses but had no effect on coronary vasoconstriction. In combination, the histamine antagonists attenuated the changes in heart rate, contractility, and CPF. The histamine-induced increase in myocardial oxygen extraction was accompanied by a significant increase in MVO2 in the presence of diphenhydramine. The ratio of the change in oxygen extraction to the change in oxygen consumption caused by histamine was significantly increased by diphenhydramine. This compensated for a histamine-induced decrement in the ratio of the change of CPF to the change in oxygen consumption. Cimetidine had no effect on the changes in coronary flow, oxygen consumption, or the above ratios. Thus, histamine causes direct coronary vasoconstriction via an H1 receptor mechanism, cardiac positive inotropy by an H2 receptor mechanism, and cardiac positive chronotropy by combined H1 and H2 mechanisms. In the presence of a histamine-induced decrease in myocardial oxygen supply, increments in oxygen demand are met by increased oxygen extraction.
Kang
Y H
YH
Graduate Program in Physiology and Neurobiology, State University, New Brunswick, New Jersey 08903.
Wei
H M
HM
Fisher
H
H
Merrill
G F
GF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D004155:Diphenhydramine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011969:Receptors, Histamine H1 / Q000187:drug effects; D011970:Receptors, Histamine H2 / Q000187:drug effects
D006633:Histamine Antagonists; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine