We have previously demonstrated a depression of airway H2-receptor function in sheep allergic to Ascaris suum antigen. To investigate whether this is a generalized defect, we studied the H1- and H2-histamine receptor functions in the pulmonary and systemic circulations of allergic and nonallergic sheep. Pulmonary arterial pressure, pulmonary arterial wedge pressure, systemic arterial pressure, and cardiac output were measured for calculation of pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) before and immediately after a rapid intrapulmonary infusion of histamine (10 μg/kg), with and without pretreatment with H1- (chlorpheniramine) and H2- (metiamide) antagonists. Histamine alone increased mean PVR to 435 and 401% of base line and decreased mean SVR by 51 and 54% in the nonallergic and allergic sheep, respectively (P < 0.001). In the nonallergic sheep following pretreatment with chlorpheniramine (selective H2 stimulation) or metiamide (selective H1 stimulation), histamine decreased SVR by 18 and 36%, respectively, suggesting that ~two-thirds of the vasodepressor response was mediated by H1-receptors and one-third by H2-receptors. Combined H1- and H2-antagonists completely blocked the histamine response. In allergic sheep the histamine-induced decrease in SVR was primarily mediated by H1-receptors, because the response was blocked by H1-antagonist, chlorpheniramine, and the H2-antagonist, metiamide, had no effect. In the pulmonary circulation selective H1-stimulation caused a similar increase in PVR in allergic (365%) and nonallergic sheep (424%), whereas selective H2-stimulation caused a significant decrease in PVR in the nonallergic group (14%) but not in the allergic group (0%). In the presence of increased pulmonary vascular tone due to hypoxia, histamine decreased mean PVR by 45% (H1-antagonist pretreatment) and 42% (combined H1- and H2-antagonists pretreatment) in the nonallergic sheep, signifying an 'atypical' H2- or H3-receptor response that was significantly greater than the 20 and 21% decreases seen in the allergic group. We conclude that in allergic sheep the H1-receptor mediated pulmonary vasoconstrictor and systemic vasodepressor responses are intact, whereas the H2-receptor mediated vasodepressor responses in the systemic circulation (typical H2) and pulmonary circulation (atypical H2) are markedly depressed.
ASJC Scopus subject areas
- Physiology (medical)