Myocardium from Patients with Heart Failure Due To Mitral and Aortic Valve Disease

Baumann, Gert; Mercader, Delia; Busch, Ulrich; Felix, Stephan B.; U, Loher; Ludwig, Liesel; Sebening, H; Heidecke, Claus Dieter; Hagl, S.; Sebening, F; Blömer, H

doi:10.1097/00005344-198307000-00017

Cited by 57 publications

(14 citation statements)

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“…In contrast to b 1 adrenoceptors, the density of H 2 receptors in failing human hearts was not changed compared with nonfailing controls [ventricular samples from transplants in Munich, Germany, where tritiated tiotipine was used in binding studies (Baumann et al, 1984)]. In isolated ventricular preparations from failing human hearts some studies did not detect a reduced PIE to histamine compared with nonfailing controls (Baumann et al, 1982(Baumann et al, , 1983(Baumann et al, , 1984, and it was suggested that H 2 agonists might be clinically useful in the treatment of heart failure. Baumann et al (1984) and Felix et al (1995) even tested a H 2 receptor agonist (impromidine) in the intensive care unit in patients and described beneficial acute effects.…”

Section: Discussionmentioning

confidence: 99%

“…1) and Hattori et al (1990Hattori et al ( , 1991. In humans, H 1 and H 2 receptors were detected early on in the atrium and ventricle [for radioligand binding, see Baumann et al (1982Baumann et al ( , 1983Baumann et al ( , 1984; for antibody and RNA expression, see Matsuda et al (2004)]. In humans, the cardiac H 2 receptors were described to mediate the PIE of exogenously applied histamine in isolated human cardiac preparations (Levi et al, 1981;Genovese et al, 1988;Zerkowski et al, 1993;Sanders et al, 1996;Thoren et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Initial Characterization of Transgenic Mice Overexpressing Human Histamine H2 Receptors

Gergs

Bernhardt

Buchwalow

et al. 2019

The Journal of Pharmacology and Experimental Therapeutics

119

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In an integrative approach, we studied the role of histamine H 2 receptors in the mouse heart. We noted that histamine, added cumulatively to the organ bath, failed to affect the force of contraction in left atrial preparations and did not change spontaneous heart rate in right atrial preparations from wildtype mice. By contrast, in the same preparations from mice that overexpressed the human H 2 receptor in a cardiac-specific way, histamine exerted concentration-and time-dependent positive inotropic and positive chronotropic effects. Messenger RNA of the human H 2 receptor was only detected in transgenic mice. Likewise, immunohistology and autoradiography only gave signals in transgenic but not in wild-type cardiac preparations. Similarly, a positive inotropic and positive chronotropic effect was observed with histamine in echocardiography of living transgenic mice and isolated perfused hearts (Langendorff preparation). Phosphorylation of phospholamban was increased in atrial and ventricular preparations from transgenic mice, but not in wild-type animals. The effects of histamine were mimicked by dimaprit and amthamine and antagonized by cimetidine. In summary, we generated a new model to study the physiologic and pathophysiologic cardiac role of the human H 2 receptor.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H2 Receptors

Gergs

Bernhardt

Buchwalow

et al. 2019

The Journal of Pharmacology and Experimental Therapeutics

119

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“…Regional differences in the actions of histamine or histamine receptor utilization by exogenous histamine in the mammalian heart are known: in rabbit left atrium, H 1 receptors are more prevalent but the PIE of histamine is mediated by H 2 receptors while in guinea pig left atrium a positive inotropic effect of histamine is mediated via H 1 receptors ( Hattori et al, 1988 ; Sakuma et al, 1988 ; Hattori et al, 1990 ; Hattori et al, 1991 ). In humans, H 1 and H 2 receptors were detected early on in atrium and ventricle (radioligand binding: Baumann et al, 1982 ; Baumann et al, 1983 ; Baumann et al, 1984 , antibody and RNA expression: Matsuda et al, 2004 ). Moreover, the human cardiac H 2 receptors were described to mediate the PIE of exogenously applied histamine in isolated human cardiac preparations (atrium: Ginsburg et al, 1980 ; Levi et al, 1981 ; Zerkowski et al, 1993 ; Sanders et al, 1996 ).…”

Section: Introductionmentioning

confidence: 99%

Histamine can be Formed and Degraded in the Human and Mouse Heart

et al. 2021

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Histamine is metabolized by several enzymes in vitro and in vivo. The relevance of this metabolism in the mammalian heart in vivo is unclear. However, histamine can exert positive inotropic effects (PIE) and positive chronotropic effects (PCE) in humans via H2-histamine receptors. In transgenic mice (H2-TG) that overexpress the human H2 receptor in cardiomyocytes but not in wild-type littermate mice (WT), histamine induced PIE and PCE in isolated left or right atrial preparations. These H2-TG were used to investigate the putative relevance of histamine degrading enzymes in the mammalian heart. Histidine, the precursor of histamine, increased force of contraction (FOC) in human atrial preparations. Moreover, histamine increased the phosphorylation state of phospholamban in human atrium. Here, we could detect histidine decarboxylase (HDC) and histamine itself in cardiomyocytes of mouse hearts. Moreover, our data indicate that histamine is subject to degradation in the mammalian heart. Inhibition of the histamine metabolizing enzymes diamine oxidase (DAO) and monoamine oxidase (MAO) shifted the concentration response curves for the PIE in H2-TG atria to the left. Moreover, activity of histamine metabolizing enzymes was present in mouse cardiac samples as well as in human atrial samples. Thus, drugs used for other indication (e.g. antidepressants) can alter histamine levels in the heart. Our results deepen our understanding of the physiological role of histamine in the mouse and human heart. Our findings might be clinically relevant because we show enzyme targets for drugs to modify the beating rate and force of the human heart.

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“…These drugs are already in use in clinical trials on patients with catecholaminerefractory heart failure (Baumann et al, 1982). Moreover, one of us has recently demonstrated that dimaprit was able to decrease the number of ventricular arrhythmias in dogs with subacute coronary thrombosis .…”

Section: Concentration Of Drugs (M)mentioning

confidence: 99%

The antianaphylactic action of histamine H₂‐receptor agonists in the guinea‐pig isolated heart

Blandina

Brunelleschi

Fantozzi

et al. 1987

British J Pharmacology

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1 The effects of histamine and of H,-and H2-receptor agonists on the response to specific antigen were studied in isolated hearts taken from actively sensitized guinea-pigs. 2 Histamine and H2-receptor agonists (dimaprit, impromidine) dose-dependently decrease the positive chronotropic and inotropic effects, and the severity of arrhythmias evoked by the challenge of sensitized hearts with specific antigen. 3 Nordimaprit and the selective H,-receptor agonist 2-pyridyl-ethyl-amine (2-PEA) did not modify the patterns of cardiac anaphylaxis. 4 The positive inotropic and chronotropic responses of the isolated heart to exogenous histamine appear to be partly reduced in the presence of dimaprit. 5 The H2-receptor agonists decrease the amount of histamine released during cardiac anaphylaxis which is increased by cimetidine, while nordimaprit and PEA were ineffective, indicating an inhibitory function afforded by H2-receptors in cardiac anaphylaxis.

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Myocardium from Patients with Heart Failure Due To Mitral and Aortic Valve Disease

Cited by 57 publications

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Initial Characterization of Transgenic Mice Overexpressing Human Histamine H2 Receptors

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H2 Receptors

Histamine can be Formed and Degraded in the Human and Mouse Heart

The antianaphylactic action of histamine H₂‐receptor agonists in the guinea‐pig isolated heart

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Myocardium from Patients with Heart Failure Due To Mitral and Aortic Valve Disease

Cited by 57 publications

References 0 publications

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H2 Receptors

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H2 Receptors

Histamine can be Formed and Degraded in the Human and Mouse Heart

The antianaphylactic action of histamine H2‐receptor agonists in the guinea‐pig isolated heart

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The antianaphylactic action of histamine H₂‐receptor agonists in the guinea‐pig isolated heart