Mechanism of histamine actions in human coronary arteries.

Abstract

Helical strips of human coronary arteries contracted in response to histamine concentration dependently, they relaxed with low concentrations and contracted with high concentrations. Treatment with cimetidine potentiated contraction in the strips with intact and damaged endothelium to a similar extent and attenuated relaxation. Removal of endothelium abolished relaxation and potentiated contraction in the cimetidine-treated strips. Methylene blue increased the contractile response to histamine in the strips with endothelium but did not alter the response in the damaged-endothelium strips. Histamine-induced relaxations in the intact strips were suppressed or abolished by treatment with ETYA, AA861, a lipoxygenase inhibitor, and by chlorpheniramine but were unaffected by indomethacin. Chlorpheniramine also abolished amine-induced contraction. It may be concluded that histamine-induced contraction in human coronary arteries is mediated by H, receptors in smooth muscle, and relaxation is mediated by H 2 receptors in smooth muscle and H, receptors in endothelium. while human coronary arteries respond with contractions. 4 Histamine constricts proximal middle cerebral arteries from dogs but dilates the distal arteries.6 These differing actions may be derived from the ability of histamine to activate histaminergic H, and H 2 receptors in vascular smooth muscle and to also activate H, receptors in endothelium, which possibly mediate the release of prostaglandin (PG) I 2 7 " or endothelium-derived relaxing factor. 3910Intravenous injections of histamine provokes coronary vasospasm in patients with variant angina," and endogenous histamine is regarded as one candidate for the genesis of the vasospasm.12 Large amount of histamine may be released by antigen-antibody reactions 13 as well as by many clinical drugs commonly used, such as morphine and d-tubocurarine.14 Similar coronary vasospasm is also produced by the amine in miniature swine in which the coronary artery is denuded and the high cholesterol diet is fed." However, the mechanism of histamine action in human coronary arteries has not yet been determined.From the Department of Pharmacology. Shiga University of Medical Sciences, Seta, Ohtsu, Japan.This paper was presented in part at the Symposium on Vasodilatation, July 1986, in Rochester, Minnesota.Address for correspondence: Dr. Noboru Toda, Department of Pharmacology, Shiga University of Medical Sciences, Seta, Ohtsu 520-21, Japan.Received June 13, 1986; accepted March 18, 1987. Therefore, the present study was undertaken to further clarify the response to histamine of coronary arteries isolated from human cadavers and to pharmacologically analyze the mechanism of its action in relation to vascular endothelium and H, and H 2 receptors. Materials and MethodsVentral, interventricular, and circumflex branches of the left coronary artery were isolated from human hearts (17 males, aged 54 to 84, and 9 females, aged 26 to 68) during autopsy up to 6 hours after death. Causes of death were stomach, rectum, lung, pharyn...

Histamine Upregulates Gene Expression of Endothelial Nitric Oxide Synthase in Human Vascular Endothelial Cells

“…Under conditions of dysfunctional eNOS, the histamine-induced vasorelaxation is converted into a contraction, which is mediated via H 1 receptors on smooth muscle cells. 9,26 Histamine-induced vasoconstriction has also been observed in atherosclerotic coronary arteries 26 -28 and may contribute to the onset of an acute coronary syndrome. Interestingly, an increased histamine content has been found in atherosclerotic coronary segments.…”

“…7 By occupying H 1 receptors on endothelial cells, histamine activates endothelial nitric oxide synthase (eNOS). 8 The nitric oxide (NO) produced by eNOS dilates all kinds of blood vessels, including human coronary arteries, 9 and has protective effects against platelet and leukocyte adhesion and smooth muscle proliferation and, thus, probably atherosclerosis. 10 However, the direct activation of eNOS by histamine represents a short-term and probably transient action of the amine.…”

The receptor mechanisms for histamine actions in proximal portion differ from those in distal portion in human coronary artery.

“…On the other hand, histamine induces a reduction of coronary vascular resistance (Vigorito et al 1986). Recently, three different histamine receptor mechanisms have been reported in the human coronary artery (Toda 1987). If these three components differ depending on the size of the coronary vessel, previously conflicting data are conceivable.…”

Pharmacological reactivity of human epicardial coronary arteries: characterization of relaxation responses to endothelium‐derived relaxing factor

“…Toda (1987) suggested that relaxation to histamine was mediated by both HI receptors on the endothelium and H2 receptors in the smooth muscle, but that the response was complicated by contraction via HI receptors on the muscle at high concentrations of histamine (0.1 4M and above). Consequently, biphasic curves have often been reported (Toda, 1987;Toda & Okamura, 1989). In this study, however, no contraction responses were observed, even at high concentrations of histamine (1-1OIM), except in the absence of endothelium, indicating that EDRF release (via endothelial HI receptors) and stimulation of the (relaxing) H2 receptors was overriding the direct constrictor effect on the smooth muscle.…”

“…Acetylcholine has been shown to be a sensitive marker of endothelial dysfunction with early atheroma (Vita et al, 1990;Zeiher et al, 1991), whilst substance P is a powerful vasodilator agent which can increase arterial diameter by up to 30% (Crossman et al, 1989). Toda (1987) demonstrated a relaxation response to substance P in human coronary artery helical strips in vitro, and release of EDRF by histamine in the same tissue. Bradykinin, the calcium ionophore A23 187 and, occasionally, acetylcholine, have also been shown to relax human coronary artery in vitro (F6rstermann et al, 1988).…”