Decreased beta-adrenergic responsiveness following hypertrophy occurs only in cardiomyocytes that also re-express beta-myosin heavy chain.
OBJECTIVE
Cardiac hypertrophy is associated with a reduction in the contractile response to beta-adrenergic stimulation, and with re-expression of foetal genes such as beta-myosin heavy chain (MHC). However, whether these two markers of pathology develop concordantly in the same individual cells or independently in different cells is not known.


RESULTS
To answer this question, we examined the beta-adrenergic response of individual beta-MHC expressing and non-expressing myocytes from hypertrophic hearts, using a previously generated mouse model (YFP/beta-MHC) in which a yellow fluorescent protein (YFP) is fused to the native beta-MHC protein allowing easy identification of beta-MHC expressing cells. Yellow fluorescent protein/beta-MHC mice were submitted to 4 weeks of transverse aortic constriction (TAC), and the contractile parameters of isolated individual myocytes in response to the beta-adrenergic agonist isoproterenol were assessed. Our results demonstrate that the decrease in isoproterenol-induced cell shortening that develops in TAC hearts occurs only in those hypertrophic myocytes that re-express beta-MHC. Hypertrophic myocytes that do not express beta-MHC have contractility indices indistinguishable from non-TAC controls.


CONCLUSIONS
These data show that the reduction of beta-adrenergic response occurs only in subsets, rather than in all myocytes, and is coincident with re-expression of beta-MHC.
Pandya
Kumar
K
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA.
Porter
Kristine
K
Rockman
Howard A
HA
Smithies
Oliver
O
D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000096:biosynthesis*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014463:Ultrasonography
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D018995:Myosin Heavy Chains; D007545:Isoproterenol