Coronary autoregulation and purine release in normoxic heart at various cytoplasmic phosphorylation potentials: disparate effects of adenosine

Y. H. Kang, Robert T. Mallet, R. Bünger

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Abstract

The impacts of energy-yielding substrates on coronary flow autoregulation, cytoplasmic phosphorylation potential {[ATP]/([ADP][Pi])} and purine nucleoside production were studied in Langendorff-perfused guinea pig hearts. The perfusion medium was substrate-free or contained glucose alone or in combination with pyruvate, lactate, acetate, or octanoate as fatty acid. When coronary flow was adjusted for myocardial oxygen consumption, only pyruvate supported near-perfect intrinsic autoregulation at highly sustained [ATP]/([ADP][Pi]) and low interstitial adenosine concentrations ([Ado]). In contrast, hearts perfused with substrate-free medium were deenergized at very high [Ado], especially at supraphysiological pressures, which markedly impaired autoregulatory vasoconstriction. Thus, efficient autoregulatory vasoconstriction was associated with high [ATP]/ ([ADP][Pi]) at low [Ado]. On the other hand, autoregulatory vasodilation at subphysiological pressures was associated with increased [Ado] and partially blocked by 28 μM theophylline demonstrating (partial) adenosine mediation. Massive accumulation of IMP, especially relative to free cytoplasmic AMP, occurred at normal intracellular pH during myocyte deenergization by substratefree perfusion. This may indicate allosteric activation of native AMP deaminase in situ, perhaps because of collapse of [ATP]/([ADP][Pi]). Similarly, rates of adenosine plus inosine release and of total purines, also including urate, exhibited non-linear sigmoidal rather than linear or rectangular hyperbolic dependences on free cytoplasmic AMP concentration (not total AMP content). Since inclusion of IMP as a co-variable of free AMP appreciably improved the sigmoidal fits, IMP appeared to be a significant precursor of released inosine in guinea pig heart.

Original languageEnglish
Pages (from-to)188-199
Number of pages12
JournalPflügers Archiv European Journal of Physiology
Volume421
Issue number2-3
DOIs
StatePublished - 1 Jun 1992

Fingerprint

Phosphorylation
Adenosine Monophosphate
Inosine Monophosphate
Adenosine
Adenosine Diphosphate
Homeostasis
Adenosine Triphosphate
Inosine
Vasoconstriction
Pyruvic Acid
Guinea Pigs
Substrates
Perfusion
AMP Deaminase
Purine Nucleosides
Pressure
Purines
Theophylline
Uric Acid
Vasodilation

Keywords

  • AMP deaminase
  • Acetate
  • Adenosine
  • Cytoplasmic phosphorylation potential
  • Fatty acids
  • Flow autoregulation
  • Free AMP
  • Guinea pig heart
  • IMP
  • Pyruvate

Cite this

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title = "Coronary autoregulation and purine release in normoxic heart at various cytoplasmic phosphorylation potentials: disparate effects of adenosine",
abstract = "The impacts of energy-yielding substrates on coronary flow autoregulation, cytoplasmic phosphorylation potential {[ATP]/([ADP][Pi])} and purine nucleoside production were studied in Langendorff-perfused guinea pig hearts. The perfusion medium was substrate-free or contained glucose alone or in combination with pyruvate, lactate, acetate, or octanoate as fatty acid. When coronary flow was adjusted for myocardial oxygen consumption, only pyruvate supported near-perfect intrinsic autoregulation at highly sustained [ATP]/([ADP][Pi]) and low interstitial adenosine concentrations ([Ado]). In contrast, hearts perfused with substrate-free medium were deenergized at very high [Ado], especially at supraphysiological pressures, which markedly impaired autoregulatory vasoconstriction. Thus, efficient autoregulatory vasoconstriction was associated with high [ATP]/ ([ADP][Pi]) at low [Ado]. On the other hand, autoregulatory vasodilation at subphysiological pressures was associated with increased [Ado] and partially blocked by 28 μM theophylline demonstrating (partial) adenosine mediation. Massive accumulation of IMP, especially relative to free cytoplasmic AMP, occurred at normal intracellular pH during myocyte deenergization by substratefree perfusion. This may indicate allosteric activation of native AMP deaminase in situ, perhaps because of collapse of [ATP]/([ADP][Pi]). Similarly, rates of adenosine plus inosine release and of total purines, also including urate, exhibited non-linear sigmoidal rather than linear or rectangular hyperbolic dependences on free cytoplasmic AMP concentration (not total AMP content). Since inclusion of IMP as a co-variable of free AMP appreciably improved the sigmoidal fits, IMP appeared to be a significant precursor of released inosine in guinea pig heart.",
keywords = "AMP deaminase, Acetate, Adenosine, Cytoplasmic phosphorylation potential, Fatty acids, Flow autoregulation, Free AMP, Guinea pig heart, IMP, Pyruvate",
author = "Kang, {Y. H.} and Mallet, {Robert T.} and R. B{\"u}nger",
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TY - JOUR

T1 - Coronary autoregulation and purine release in normoxic heart at various cytoplasmic phosphorylation potentials

T2 - disparate effects of adenosine

AU - Kang, Y. H.

AU - Mallet, Robert T.

AU - Bünger, R.

PY - 1992/6/1

Y1 - 1992/6/1

N2 - The impacts of energy-yielding substrates on coronary flow autoregulation, cytoplasmic phosphorylation potential {[ATP]/([ADP][Pi])} and purine nucleoside production were studied in Langendorff-perfused guinea pig hearts. The perfusion medium was substrate-free or contained glucose alone or in combination with pyruvate, lactate, acetate, or octanoate as fatty acid. When coronary flow was adjusted for myocardial oxygen consumption, only pyruvate supported near-perfect intrinsic autoregulation at highly sustained [ATP]/([ADP][Pi]) and low interstitial adenosine concentrations ([Ado]). In contrast, hearts perfused with substrate-free medium were deenergized at very high [Ado], especially at supraphysiological pressures, which markedly impaired autoregulatory vasoconstriction. Thus, efficient autoregulatory vasoconstriction was associated with high [ATP]/ ([ADP][Pi]) at low [Ado]. On the other hand, autoregulatory vasodilation at subphysiological pressures was associated with increased [Ado] and partially blocked by 28 μM theophylline demonstrating (partial) adenosine mediation. Massive accumulation of IMP, especially relative to free cytoplasmic AMP, occurred at normal intracellular pH during myocyte deenergization by substratefree perfusion. This may indicate allosteric activation of native AMP deaminase in situ, perhaps because of collapse of [ATP]/([ADP][Pi]). Similarly, rates of adenosine plus inosine release and of total purines, also including urate, exhibited non-linear sigmoidal rather than linear or rectangular hyperbolic dependences on free cytoplasmic AMP concentration (not total AMP content). Since inclusion of IMP as a co-variable of free AMP appreciably improved the sigmoidal fits, IMP appeared to be a significant precursor of released inosine in guinea pig heart.

AB - The impacts of energy-yielding substrates on coronary flow autoregulation, cytoplasmic phosphorylation potential {[ATP]/([ADP][Pi])} and purine nucleoside production were studied in Langendorff-perfused guinea pig hearts. The perfusion medium was substrate-free or contained glucose alone or in combination with pyruvate, lactate, acetate, or octanoate as fatty acid. When coronary flow was adjusted for myocardial oxygen consumption, only pyruvate supported near-perfect intrinsic autoregulation at highly sustained [ATP]/([ADP][Pi]) and low interstitial adenosine concentrations ([Ado]). In contrast, hearts perfused with substrate-free medium were deenergized at very high [Ado], especially at supraphysiological pressures, which markedly impaired autoregulatory vasoconstriction. Thus, efficient autoregulatory vasoconstriction was associated with high [ATP]/ ([ADP][Pi]) at low [Ado]. On the other hand, autoregulatory vasodilation at subphysiological pressures was associated with increased [Ado] and partially blocked by 28 μM theophylline demonstrating (partial) adenosine mediation. Massive accumulation of IMP, especially relative to free cytoplasmic AMP, occurred at normal intracellular pH during myocyte deenergization by substratefree perfusion. This may indicate allosteric activation of native AMP deaminase in situ, perhaps because of collapse of [ATP]/([ADP][Pi]). Similarly, rates of adenosine plus inosine release and of total purines, also including urate, exhibited non-linear sigmoidal rather than linear or rectangular hyperbolic dependences on free cytoplasmic AMP concentration (not total AMP content). Since inclusion of IMP as a co-variable of free AMP appreciably improved the sigmoidal fits, IMP appeared to be a significant precursor of released inosine in guinea pig heart.

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KW - Acetate

KW - Adenosine

KW - Cytoplasmic phosphorylation potential

KW - Fatty acids

KW - Flow autoregulation

KW - Free AMP

KW - Guinea pig heart

KW - IMP

KW - Pyruvate

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U2 - 10.1007/BF00374826

DO - 10.1007/BF00374826

M3 - Article

C2 - 1528716

AN - SCOPUS:0026670383

VL - 421

SP - 188

EP - 199

JO - Pflügers Archiv European Journal of Physiology

JF - Pflügers Archiv European Journal of Physiology

SN - 0031-6768

IS - 2-3

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