PMID- 1653120
OWN - NLM
STAT- MEDLINE
DCOM- 19911004
LR  - 20190623
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 84
IP  - 3
DP  - 1991 Sep
TI  - Differences in beta-adrenergic neuroeffector mechanisms in ischemic versus 
      idiopathic dilated cardiomyopathy.
PG  - 1024-39
AB  - BACKGROUND: We measured the content and activities of components of the 
      beta-adrenergic receptor-G protein-adenylate cyclase complex and adrenergic 
      neurotransmitter levels in left and right ventricular myocardial preparations 
      derived from 77 end-stage failing human hearts from patients with idiopathic 
      dilated cardiomyopathy (IDC) or ischemic dilated cardiomyopathy (ISCDC). METHODS 
      AND RESULTS: The results were compared with data obtained in 21 nonfailing hearts 
      removed from organ donors. Compared with ISCDC ventricles, IDC left and right 
      ventricles exhibited a greater degree of total beta- or beta 1-receptor 
      downregulation. In contrast, compared with IDC right ventricles, isolated tissue 
      preparations of ISCDC right ventricles exhibited a greater degree of 
      subsensitivity to the inotropic effect of isoproterenol, indicating a relatively 
      greater degree of functional uncoupling of right ventricular ISCDC beta-receptors 
      from mechanical response. In addition, relative to IDC left ventricles, 
      preparations of ISCDC left ventricle exhibited greater subsensitivity to 
      beta-agonist-mediated adenylate cyclase stimulation, indicating functional 
      uncoupling of left ventricular ISCDC beta-receptors from cyclic AMP generation. 
      The uncoupling of beta-receptors in ISCDC left and right ventricles may have been 
      a result of abnormalities in G protein activation of adenylate cyclase; compared 
      with age- and cardiac function-matched respective left or right IDC ventricles, 
      ISCDC left ventricles exhibited less stimulation of adenylate cyclase by NaF or 
      forskolin but no change in Mn2+ stimulation, whereas ISCDC right ventricles 
      exhibited less stimulation by the nonhydrolyzable guanine nucleotide Gpp (NH)p. 
      Also, IDC right ventricles exhibited a "selective" (not present in IDC left 
      ventricles or ISCDC ventricles) decrease in stimulation of adenylate cyclase by 
      Mn2+. Tissue neurotransmitter levels and pertussis toxin-catalyzed ADP 
      ribosylation were altered to similar extents in IDC and ISCDC: CONCLUSIONS: These 
      data indicate that potentially important differences exist in the regulatory 
      behavior of components of the beta-adrenergic receptor-G protein-adenylate 
      cyclase complex in IDC versus ISCDC, differences that presumably relate to the 
      distinct pathophysiologies of these two types of heart muscle disease.
FAU - Bristow, M R
AU  - Bristow MR
AD  - Heart Failure Treatment Program, University of Utah, Salt Lake City.
FAU - Anderson, F L
AU  - Anderson FL
FAU - Port, J D
AU  - Port JD
FAU - Skerl, L
AU  - Skerl L
FAU - Hershberger, R E
AU  - Hershberger RE
FAU - Larrabee, P
AU  - Larrabee P
FAU - O'Connell, J B
AU  - O'Connell JB
FAU - Renlund, D G
AU  - Renlund DG
FAU - Volkman, K
AU  - Volkman K
FAU - Murray, J
AU  - Murray J
AU  - et al.
LA  - eng
GR  - HD-39719/HD/NICHD NIH HHS/United States
GR  - HL-13108/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Catecholamines)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Neuropeptide Y)
RN  - 0 (Receptors, Adrenergic, beta)
RN  - 83498-72-0 (Iodocyanopindolol)
RN  - BJ4HF6IU1D (Pindolol)
RN  - EC 2.7.3.2 (Creatine Kinase)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
SB  - IM
MH  - Adenylyl Cyclases/metabolism
MH  - Adult
MH  - Cardiomyopathy, Dilated/*physiopathology
MH  - Catecholamines/metabolism
MH  - Creatine Kinase/metabolism
MH  - Down-Regulation/physiology
MH  - Female
MH  - GTP-Binding Proteins/metabolism
MH  - Heart/*innervation
MH  - Humans
MH  - Iodine Radioisotopes
MH  - Iodocyanopindolol
MH  - Male
MH  - Middle Aged
MH  - Neuropeptide Y/metabolism
MH  - Pindolol/analogs & derivatives
MH  - Receptors, Adrenergic, beta/*physiology
EDAT- 1991/09/01 00:00
MHDA- 1991/09/01 00:01
CRDT- 1991/09/01 00:00
PHST- 1991/09/01 00:00 [pubmed]
PHST- 1991/09/01 00:01 [medline]
PHST- 1991/09/01 00:00 [entrez]
AID - 10.1161/01.cir.84.3.1024 [doi]
PST - ppublish
SO  - Circulation. 1991 Sep;84(3):1024-39. doi: 10.1161/01.cir.84.3.1024.