Influence of Serotonin 5-HT Receptors on Responses to Cardiac Stressors in Transgenic Mouse Models.

The current study aimed to deepen our knowledge on the role of cardiac 5-HT receptors under pathophysiological conditions. To this end, we used transgenic (TG) mice that overexpressed human 5-HT receptors solely in cardiac myocytes (5-HT-TG mice) and their wild-type (WT) littermates that do not have functional cardiac 5-HT receptors as controls. We found that an inflammation induced by lipopolysaccharide (LPS) was detrimental to cardiac function in both 5-HT-TG and WT mice.

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

Histamine is metabolized by several enzymes and . The relevance of this metabolism in the mammalian heart is unclear. However, histamine can exert positive inotropic effects (PIE) and positive chronotropic effects (PCE) in humans via H-histamine receptors.

Initial Characterization of Stressed Transgenic Mice With Cardiomyocyte-Specific Overexpression of Protein Phosphatase 2C.

As part of our ongoing studies on the potential pathophysiological role of serine/threonine phosphatases (PP) in the mammalian heart, we have generated mice with cardiac-specific overexpression of PP2Cβ (PP2C-TG) and compared them with littermate wild type mice (WT) serving as a control. Cardiac fibrosis was noted histologically in PP2C-TG. Collagen 1a, interleukin-6 and the natriuretic peptides ANP and BNP were augmented in PP2C-TG vs.

Characterization of Stressed Transgenic Mice Overexpressing H-Histamine Receptors in the Heart.

We studied transgenic mice with cardiac-specific overexpression of H-histamine receptors (H-TG) by using the -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 high histamine concentrations.

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H Receptors.

In an integrative approach, we studied the role of histamine H 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 wild-type mice. By contrast, in the same preparations from mice that overexpressed the human H receptor in a cardiac-specific way, histamine exerted concentration- and time-dependent positive inotropic and positive chronotropic effects.