143 SYSTEMIC VASCULAR HISTAMINE RECEPTORS

Abstract

Histamine H1 - and H2- receptor mediated changes in systemic vascular resistance were evaluated in 10 newborn lambs (0-3 days of age). Lambs were anesthetized with chloralose and instrumented to allow for continuous measurement of systemic vascular resistance (SVR), cardiac output (CO) and heart rate (HR). Histamine was injected into the main pulmonary artery in doses ranging from 0.01 to 1.0 μg/kg of histamine base. In each lamb, histamine dose response curves were generated for SVR, HR and stroke volume (SV) and repeated in 6 lambs after the administration of the H1-receptor antagonist, diphenhydramine, and/or the H2-receptor antagonist, cimetidine. The major effect of histamine on SVR, a decrease of 20-22%, occurred at a dosage of 0.6 μg/kg. No effect was noted on SVR below a dose of 0.05 μg/kg. HR increased by 10-15% at these same dosages. No effect on SV was observed. The H1-receptor antagonist decreased the SVR response significantly and had a small effect on the HR response. The H2-receptor antagonist had no effect on the SVR response and a major effect on the HR response. Thus, H1-receptors appear to mediate systemic vascular relaxation in the newborn lamb and H2-receptors mediate cardiotonic changes. The dosage range required to produce these effects was an order of magnitude larger than those we previously reported as having significant effects on pulmonary vascular resistance. In addition H2-receptors appear to be less important in the SVR response of newborns as compared to adults.