Beneficial and detrimental actions of histamine H1- and H2-receptor antagonists in circulatory shock.

Abstract

This study explores the use of both histamine H(1)- and H(2)-receptor antagonists in two different forms of circulatory shock and suggests that histamine may be involved in more than one way in the pathophysiology of circulatory shock. Various single doses of diphenhydramine, chlorpheniramine, promethazine, and burimamide were administered intravenously to Wistar rats subjected to hemorrhagic or bowel ischemia shock. Cumulative survival and mortality, as well as arterial blood pressures and microhematocrits, were monitored. Pretreatment of the animals with the three different H(1)-receptor antagonists exerted significant protection against both forms of shock. Rats pretreated with the H(2)-receptor antagonist, burimamide, demonstrated an exacerbated mortality after induction of shock. Animals pretreated with H(1)-receptor antagonists showed significantly higher mean arterial blood pressure, greater compensatory rebound of blood pressure after induction of shock, and greater responses to transfusion after hemorrhage than control, shocked animals. Similarly, rats pretreated with the H(1)-receptor blockers demonstrated significantly greater compensatory hemodilution which continued late in shock. In marked contrast, rats pretreated with burimamide exhibited opposite effects after hemorrhage and bowel ischemia, i.e., significant falls in blood pressure, lack of compensatory rebound and response to transfusion of shed blood, and a progressive hemoconcentration. This report clearly demonstrates beneficial actions of histamine H(1)-receptor antagonists and detrimental effects of H(2)-receptor antagonists on survival and other parameters in these forms of circulatory shock.