title: Chronic alpha-adrenergic receptor stimulation modulates the contractile phenotype of cardiac myocytes in vitro.
abstract: BACKGROUND
  Heart failure is characterized by contractile dysfunction of the myocardium and elevated sympathetic activity. We tested the hypothesis that chronic alpha-adrenergic (alpha-ADR) stimulation modifies the molecular and contractile phenotype of cardiac myocytes.
  
  
  RESULTS
  Adult rat ventricular myocytes in culture were exposed to alpha-ADR stimulation (norepinephrine + propranolol) for 48 hours. alpha-ADR stimulation decreased the mRNAs for sarcoplasmic reticulum Ca(2+)-ATPase and Ca(2+) release channel by 56% and 52%, respectively, and increased mRNA and protein for the Na(+)-Ca(2+) exchanger by 70% and 39%, respectively. After washout of the alpha-ADR agonist, simultaneous measurement of [Ca(2+)](i) transients with fura 2 and myocyte shortening by video edge-detection showed that [Ca(2+)](i) amplitude and myocyte shortening were decreased in alpha-ADR-treated myocytes, and the time to peak and time from peak to 80% decline of both [Ca(2+)](i) and myocyte shortening were increased. The concentration-response curve for myocyte shortening by the Na(+) channel activator veratridine was shifted leftward in alpha-ADR-stimulated myocytes (EC(50), 21.6+/-4.6 versus 105.8+/-10.5 nmol/L, P:<0.001).
  
  
  CONCLUSIONS
  Chronic alpha-ADR stimulation of cardiac myocytes causes decreases in the expression of sarcoplasmic reticulum Ca(2+)-ATPase and the Ca(2+) release channel that are associated with decreases in [Ca(2+)](i) and contractility. alpha-ADR stimulation simultaneously increases Na(+)-Ca(2+) exchanger expression, thereby increasing sensitivity to intracellular Na(+).
authors.affiliation: Cardiovascular Section, Boston University Medical Center, Myocardial Biology Unit and Cardiac Muscle Research Laboratory, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: N
authors.initials: N
authors.lastname: Satoh
authors.forename: T M
authors.initials: TM
authors.lastname: Suter
authors.forename: R
authors.initials: R
authors.lastname: Liao
authors.forename: W S
authors.initials: WS
authors.lastname: Colucci
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016257:Fura-2; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010641:Phenotype; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D015220:Calcium Channels; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D014701:Veratridine; D011433:Propranolol; D000252:Calcium-Transporting ATPases; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine