H₁ AND H₂ HISTAMINE ACTIONS ON LUNG VESSELS; THEIR RELEVANCE TO HYPOXIC VASOCONSTRICTION

Abstract

Pulmonary vasomotor actions of histamine and the possible relationship of histamine to hypoxic pulmonary vasconstriction were studied in anaesthetized cats with one lobe of lung perfused at constant flow and in isolated perfused rat and ferret lungs. In the cat histamine caused dilatation, biphasic responses and constriction with increasing doses. Histamine induced dilatation was better demonstrated during hypoxic vasoconstriction and was reduced by an H2 histamine antagonist; constriction with histamine was abolished by an H1 antagonist. kistamine also caused both vasodilatation and vasoconstriction in ferret lungs. A mast cell stabilizing agent had no effect on hypoxic pulmonary vasoconstriction in cats or rats. This response was unaffected in cats but greatly reduced in rats and ferrets by cyproheptadine, a combined histamine and 5-hydroxytryptamine inhibitor. It was unaffected in cats but abolished in ferrets by an H1 histamine inhibitor. It was again unaffected in cats but greatly reduced in rats and ferrets bv an H2 histamine inhibitor. These species differences may reflect differences in mechanism but more probably reflect nonspecific effects of the inhibitors in certain circumstances. However, when drugs nearly abolished hypoxic vasoconstriction, ATP still caused vasoconstriction.Histamine constricts pulmonary vascular and alveolar duct smooth muscle. It may be released from mast cells and discharged into pulmonary veins during hypoxia [Haas and Bergofsky, 1972]. In rats the pulmonary vasoconstriction caused by hypoxia was modified by drugs inhibiting, releasing or enhancing histamine [Hauge, 1968]. It has therefore been proposed that histamine might be a transmitter responsible for hypoxic vasoconstriction. The hypothesis cannot be sustained in its original form. Histamine has been shown to cause pulmonary vasodilatation as well as vasoconstriction [Dawes and Mott, 1962;Barer, 1966;Shaw, 1971;Silove and Simcha, 1973;Howard, Barer, Thompson, Warren, Abbott and Mungall, 1975;Thompson, Barer and Shaw, 1976], and the drugs affecting hypoxic vasoconstriction in the rat are ineffective in other species [Barer and McCurrie, 1969;Howard et al, 1975;Tucker, Weir, Reeves and Grover, 1976].Our objective was first to clarify the two actions of histamine in terms of dose-response relationships and by the use of antagonistic drugs to see whether they are attributable to the two types of histamine receptor [Ash and Schild, 1966]. Second, we tried to clarify the relation ofhistamine to hypoxic pulmonary vasoconstriction. We used three species. We compared the cat in which H1 histamine receptor antagonists have not abolished hypoxic vasoconstriction

Thromboxane and histamine mediate PVR elevation during xenogeneic pig lung perfusion with human blood

“…The role of histamine H1‐ and H2‐receptors in the lung has previously been investigated. Various studies suggest that increased lung permeability and vasodilatation are mediated by H2 receptors, while the bronchoconstriction is ascribed primarily to an H1‐receptor mechanism . However, H1‐receptors have also been implicated in vasoconstriction in a lung circuit at higher histamine concentrations .…”

The principal pathways involved in the in vivo modulation of hypoxic pulmonary vasoconstriction, pulmonary arterial remodelling and pulmonary hypertension

“…Treatment with a H2 receptor antagonist was without effect on the acute phase of the HPV response in cats (Barer et al . ), but potentiated the response in dogs (Tucker et al . ).…”

Histamine receptors of the microvascular endothelium revealed in situ with a histamine-ferritin conjugate: characteristic high-affinity binding sites in venules.

“…Histamine participates in a number of physiological processes particularly those of the cardiovascular system (1,5,6,9,32,34) and is largely involved in inflammatory and anaphylactic reaction (3,4). As identified on a physiological and pharmacological basis, its effects are mediated by two types of receptors: H, receptors, specifically inhibited by classical antihistamines such as mepyramine, and H2 receptors, blocked by antagonists such as cimetidine (8,19,35).…”