PMID- 7943405
OWN - NLM
STAT- MEDLINE
DCOM- 19941118
LR  - 20171213
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 267
IP  - 4 Pt 2
DP  - 1994 Oct
TI  - Mechanisms mediating responsiveness to beta-adrenergic stimulation after coronary 
      reperfusion in conscious dogs.
PG  - H1578-88
AB  - The goal of this study was to assess beta-adrenergic receptor (beta-AR) signaling 
      mechanisms in mediating physiological responses to sympathomimetic amines after 
      45 min coronary artery occlusion followed by 45 min reperfusion. At this time, 
      isoproterenol (Iso) infusion (0.1 microgram/kg-1.min-1, n = 5) increased percent 
      wall thickening in previously ischemic subendocardium (Endo) more than in 
      nonischemic Endo (12.6 +/- 1.2 vs. 7.2 +/- 0.6%, P < 0.05), whereas forskolin (25 
      nmol.kg-1.min-1, n = 6) elicited the opposite effect (3.6 +/- 0.6 vs. 10.4 +/- 
      2.8%, P < 0.05). During Iso and forskolin infusions increases in regional 
      myocardial blood flow in the previously ischemic zone were similar to the 
      nonischemic zone. In all groups, total beta-AR density was depressed in 
      previously ischemic Endo compared with nonischemic Endo (65 +/- 7 vs. 82 +/- 8 
      fmol/mg, P < 0.05), but the fraction of beta-AR binding agonist with high 
      affinity increased (82 +/- 4 vs. 49 +/- 1%, P < 0.05). The changes in beta-AR 
      were associated with a decrease in Iso-stimulated adenylyl cyclase (22 +/- 8%), a 
      decrease in guanosine 5'-triphosphate (GTP)-stimulatory protein (Gs) (23 +/- 6%), 
      and a decrease in inhibitory G proteins (16 +/- 4%). However, regional Endo 
      functional responsiveness to beta-AR stimulation was enhanced in reperfused 
      myocardium in response to Iso but not to forskolin. Thus the mechanism of 
      increased number of beta-AR binding agonist with high affinity in previously 
      ischemic myocardium predominated over persistent downregulation of total beta-AR 
      density and reductions in Gs and adenylyl cyclase activity and correlated best 
      with the physiological response to beta-AR stimulation. These data may also 
      suggest that Iso exerts an action distal to adenylyl cyclase in previously 
      ischemic myocardium.
FAU - Kiuchi, K
AU  - Kiuchi K
AD  - Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, 
      Boston 02115.
FAU - Shen, Y T
AU  - Shen YT
FAU - Vatner, S F
AU  - Vatner SF
FAU - Vatner, D E
AU  - Vatner DE
LA  - eng
GR  - HL-33065/HL/NHLBI NIH HHS/United States
GR  - HL-37404/HL/NHLBI NIH HHS/United States
GR  - HL-45332/HL/NHLBI NIH HHS/United States
GR  - etc.
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  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Adrenergic, beta)
RN  - 1F7A44V6OU (Colforsin)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - L628TT009W (Isoproterenol)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Colforsin/pharmacology
MH  - Coronary Vessels/*physiology
MH  - Dogs
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Female
MH  - GTP-Binding Proteins/analysis/*biosynthesis
MH  - Heart/drug effects/physiology/*physiopathology
MH  - Heart Rate/drug effects
MH  - Hemodynamics/*drug effects/physiology
MH  - Isoproterenol/*pharmacology
MH  - Male
MH  - Molecular Sequence Data
MH  - Myocardial Ischemia/*physiopathology
MH  - *Myocardial Reperfusion
MH  - Myocardium/metabolism
MH  - Peptide Fragments/immunology
MH  - Receptors, Adrenergic, beta/*physiology
MH  - Signal Transduction
MH  - Time Factors
MH  - Ventricular Function, Left/drug effects/physiology
EDAT- 1994/10/01 00:00
MHDA- 1994/10/01 00:01
CRDT- 1994/10/01 00:00
PHST- 1994/10/01 00:00 [pubmed]
PHST- 1994/10/01 00:01 [medline]
PHST- 1994/10/01 00:00 [entrez]
AID - 10.1152/ajpheart.1994.267.4.H1578 [doi]
PST - ppublish
SO  - Am J Physiol. 1994 Oct;267(4 Pt 2):H1578-88. doi: 
      10.1152/ajpheart.1994.267.4.H1578.