title: Cardiac-directed adenylyl cyclase expression improves heart function in murine cardiomyopathy.
abstract: BACKGROUND
  We tested the hypothesis that increased cardiac myocyte adenylyl cyclase (AC) content increases cardiac function and response to catecholamines in cardiomyopathy.
  
  
  RESULTS
  Transgenic mice with cardiac-directed expression of AC type VI (ACVI) were crossbred with mice with cardiomyopathy induced by cardiac-directed Gq expression. Gq mice had dilated left ventricles, reduced heart function, decreased cardiac responsiveness to catecholamine stimulation, and impaired beta-adrenergic receptor (betaAR)-dependent and AC-dependent cAMP production. Gq/AC mice showed improved basal cardiac function in vivo (P=0.01) and ex vivo (P<0.0005). When stimulated through the betaAR, cardiac responsiveness was increased (P=0.02), and cardiac myocytes showed increased cAMP production in response to isoproterenol (P=0.03) and forskolin (P<0.0001).
  
  
  CONCLUSIONS
  Increasing myocardial ACVI content in cardiomyopathy restores cAMP-generating capacity and improves cardiac function and responsiveness to betaAR stimulation.
authors.affiliation: Department of Medicine, VAMC-San Diego and University of California, San Diego, CA, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Roth
authors.forename: M H
authors.initials: MH
authors.lastname: Gao
authors.forename: N C
authors.initials: NC
authors.lastname: Lai
authors.forename: J
authors.initials: J
authors.lastname: Drumm
authors.forename: N
authors.initials: N
authors.lastname: Dalton
authors.forename: J Y
authors.initials: JY
authors.lastname: Zhou
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: D
authors.initials: D
authors.lastname: Entrikin
authors.forename: H K
authors.initials: HK
authors.lastname: Hammond
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy*; D000242:Cyclic AMP / Q000096:biosynthesis; D004452:Echocardiography; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D015316:Genetic Therapy; D006334:Heart Function Tests; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D019076:Transgenes / Q000502:physiology
chemical_list: D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol