Characterization of H1- and H2-receptor function in pulmonary and systemic circulations of sheep

Abstract

We investigated the histamine H1- and H2-receptor function in the pulmonary and systemic circulations of sheep by in vivo and in vitro techniques. Combined H1 and H2 stimulation (by intravenous histamine) in vivo increased pulmonary vascular resistance (PVR) to 435% of base line and decreased systemic vascular resistance (SVR) to 49% of base line. Selective H2 stimulation (histamine after chlorpheniramine pretreatment) decreased PVR and SVR to 86 and 82% at base line, respectively, while selective H1 stimulation (histamine after metiamide pretreatment) increased PVR to 424% of base line and decreased SVR to 64% of base line. Combined H1- and H2-antagonist pretreatment completely blocked the effects of histamine on SVR, while PVR still decreased to 85% of base line, suggesting a mild "atypical" H2-receptor response in the pulmonary circulation under conditions of resting vascular tone. With increased pulmonary vascular tone (hypoxia), histamine decreased PVR to 55% (H1-antagonist pretreatment) and to 58% (combined H1- and H2-antagonist pretreatment) of posthypoxia values, respectively, demonstrating a marked atypical H2-receptor response. In vitro, both pulmonary arterial and venous strips showed a contractile dose-response to histamine, which was blocked by the H1-antagonist pyrilamine (mepyramine). In precontracted strips, both histamine and the H2-agonists (dimaprit and impromidine) elicited a relaxant response, which was neither blocked by H1-antagonist alone nor by combined H1- and H2-antagonists. We conclude that in sheep the histamine-induced pulmonary vasoconstrictor response is mediated by H1-receptors, while the pulmonary vasodepressor response is mediated by atypical H2-receptors. The systemic vasodepressor response is mediated by both H1- and typical H2-receptors.

Contractions to Histamine in Pulmonary and Mesenteric Arteries from Endotoxemic Rabbits: Modulation by Vascular Expressions of Inducible Nitric-Oxide Synthase and Histamine H1-Receptors

“…Thus, histamine does not seem to be capable of producing eNOS-dependent relaxation in the rabbit vessels employed herein. Our result with mesenteric arteries is in contrast to the in vivo study where histamine causes systemic vasodilatation (Ahmed et al, 1982). The effects of histamine on vascular tone may vary depending on the type of vessel (conductance or resistance) being studied.…”

“…A significant increase in the plasma histamine level has been also reported in a rat model of ARDS produced by phospholipase A 2 injection (Stömmer and Steinmann, 1989). Histamine can affect both pulmonary and systemic vascular responses (Ahmed et al, 1982), lung mechanics (Hutchinson et al, 1982), and pulmonary microvascular permeability (Brigham et al, 1980). Experimental studies using the porcine model of septic ARDS have shown that treatment with histamine receptor blockers in combination with blockade of a number of inflammatory mediators ameliorates abnormal parameters and improves animal survival time (Sielaff et al, 1987;Byrne et al, 1990).…”

“…It has been shown that H 1 -and H 2 -receptors mediate pulmonary vasoconstriction and vasodilatation, respectively, but stimulation of either receptor produces systemic vasodilatation (Ahmed et al, 1982). Thus, histamine may contribute to the pulmonary hypertension (by H 1 -receptor-mediated vasoconstriction) that occurs in septic ARDS.…”

H1‐ and H2‐receptor characterization in the tracheal circulation of sheep

“…This possibility was not tested, since in the sheep that had a triphasic response to histamine the late dilatation was abolished by bilateral cervical vagotomy, suggesting that the effect depended on tonic activity in the vagus nerve. However, the time to reach maximum response was between 3 and 5min which is unlikely to be a reflex action on C-fibres or irritant receptors in either the trachea or the lungs (Coleridge & Coleridge, 1986 (Salonen et al, 1988 Hl-receptors (Tucker et al, 1975;Ahmed & King, 1986), but a H1-receptor-mediated vasoconstriction of the systemic tracheal vasculature is an unusual response since histamine reduces systemic arterial blood pressure in dogs and sheep (Tucker et al, 1975;Ahmed et al, 1982), dilates the bronchial artery of the sheep Link et al, 1985) and dilates the tracheal vasculature in dogs (Laitinen et al, 1987c,d).…”

Fetal Pulmonary Vasodilation by Histamine: Response to H(1) and H(2) Stimulation

“…Stimulation of these two receptors results in different responses in the adult animal depending upon whether the stimulation occurs under normoxic or hypoxic conditions [3][4][5], In the neonatal period the effect of Hi or H2 stimu…”