RT Journal Article SR Electronic T1 Characterization of stressed transgenic mice overexpressing H2-histamine receptors in the heart JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP JPET-AR-2020-000063 DO 10.1124/jpet.120.000063 A1 Ulrich Gergs A1 Uwe Kirchhefer A1 Fabian Bergmann A1 Bernhard Künstler A1 Natascha Mißlinger A1 Bastian Au A1 Mareen Mahnkopf A1 Hartmut Wache A1 Joachim Neumann YR 2020 UL http://jpet.aspetjournals.org/content/early/2020/06/19/jpet.120.000063.abstract AB We studied transgenic mice with cardiac-specific overexpression of H2-histamine receptors (H2-TG) by using the alpha myosin heavy chain promoter. We wanted to address whether this overexpression would protect the heart against paradigmatic stressors. To this end, we studied isolated atrial preparations in an organ bath under normoxic and hypoxic conditions and after prolonged exposure to prolonged high histamine concentrations. Moreover, we assessed cardiac function using echocardiography in mice with cardiac hypertrophy because of overexpression of the catalytic subunit of PP2A (PP2A-TG) in the heart (H2-TGxPP2A-TG=DT) or H2-TG with cardiac systolic failure because of treatment of mice with lipopolysaccharides (LPS). Furthermore, the effect of ischemia and reperfusion were studied in isolated perfused hearts (Langendorff-mode) of H2-TG. We detected evidence for the protective role of the overexpressed H2-histamine receptors in the contractile dysfunction of double transgenic (DT) and isolated atrial preparations subjected to hypoxia. In contrast, we noted the detrimental role of H2-histamine receptor overexpression against ischemia (Langendorff perfusion) and LPS-induced systolic heart failure. Hence, the role of H2-histamine receptors in the heart is context sensitive: the results differ between hypoxia (in atrium) and ischemia (perfused whole heart) as well as between genetically induced hypertrophy (DT) and toxin-induced heart failure (LPS). The underlying molecular mechanisms for the protective or detrimental roles of H2-histamine receptor overexpression in the mammalian heart remain to be elucidated.