title: β-Adrenergic signaling and response to pressure overload in transgenic mice with cardiac-specific overexpression of inducible NO synthase.
abstract: The role of iNOS induction in the context of cardiac hypertrophy and heart failure is still not fully understood. We have used transgenic mice with cardiac specific overexpression of iNOS (tg-iNOS) to investigate the consequences of high level NO formation on cardiac function in vivo and the response to chronic pressure overload. Conductance manometry was used to analyze cardiac function of wild type (WT) and tg-iNOS mice under basal conditions and β-adrenergic stimulation. To investigate the influence of iNOS on cardiac function in hypertrophied hearts, transversal aortic constriction was performed. Despite a high level of cardiac NO formation tg-iNOS mice showed almost normal LV function under basal conditions. The cardiac response to β-adrenergic stimulation, however, was completely abolished. Acute NOS inhibition led to an instantaneous recovery of the inotropic response to catecholamines in tg-iNOS mice. Chronic pressure overload induced a similar extent of cardiac hypertrophy in WT and tg-iNOS hearts. LV function, however, was more compromised in tg-iNOS hearts as revealed by a decreased contractility and cardiac output.
  
  
  CONCLUSIONS
  a high level of cardiac NO formation does not induce heart failure per se but severely enhances the functional depression in response to pressure overload. This effect could be due to the tonic impairment of the cardiac β-adrenergic response.
authors.affiliation: Institut für Herz- and Kreislaufphystologie, Heinrich-Heine-Universität Düsseldorf, Postfach 101007, 40001 Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Reinartz
authors.forename: Andrei
authors.initials: A
authors.lastname: Molojavyi
authors.forename: Sarah
authors.initials: S
authors.lastname: Moellendorf
authors.forename: Thomas
authors.initials: T
authors.lastname: Hohlfeld
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Heger
authors.forename: Axel
authors.initials: A
authors.lastname: Gödecke
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction; D017725:Ventricular Pressure
chemical_list: D017382:Reactive Oxygen Species; D011943:Receptors, Adrenergic, beta; D052247:Nitric Oxide Synthase Type II