The influence of chemical factors on the coronary circulation

Hilton, Robert; Eichholtz, Fritz

doi:10.1113/jphysiol.1925.sp002200

Cited by 177 publications

(54 citation statements)

References 7 publications

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“…It has become clear that the resistance of the coronary vasculature is regulated T. FORRESTER AND C. A. WILLIAMIS by the metabolic demands of the tissue and it is most probable that the primary stimulus comes from the lowered oxygen tension in the fluid environment of the myocardial cells (Hilton & Eichholtz, 1925). It is postulated that the cells release substances which cause local blood vessels to dilate, allowing delivery of more oxygen to the tissues.…”

Section: Introductionmentioning

confidence: 99%

Release of adenosine triphosphate from isolated adult heart cells in response to hypoxia

Forrester

Williams

1977

The Journal of Physiology

192

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SUMMARY1. Adult rat heart cells were isolated enzymically and ATP was identified in the cell suspension using the firefly luminescence technique. Adenosine 5'-triphosphate (ATP) was not detected from cell suspensions obtained from hearts which had been left asystolic for 10 min. 4am/min at 370 C. Q10 was found to be 4 between 25 and 370 C. Enzyme activity remained unaffected by either hypoxic conditions or ouabain.5. If these amounts of ATP are released from myocardial cells rendered hypoxic in vivo, then it must be concluded that ATP plays a principal role in the local control of myocardial blood flow.6. It is proposed that release of ATP occurs through the sarcolemma from an intracellular pool, and that alteration of the configuration of structural membrane protein controls the amounts of ATP extruded.

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Section: Introductionmentioning

confidence: 99%

Release of adenosine triphosphate from isolated adult heart cells in response to hypoxia

Forrester

Williams

1977

The Journal of Physiology

192

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“…Cardiac output and coronary blood flow also may increase in the absence of any reduction in tissue oxygen tension when metabolic changes like those occurring in hypoxia are produced by cyanide (1,2). Thus, these hemodynamic changes could be attributed, at least in part, to alterations in metabolite contents typical ofhypoxia.…”

Section: Introductionmentioning

confidence: 99%

Metabolic control of circulation. Effects of iodoacetate and fluoroacetate.

Liang¹

1977

J. Clin. Invest.

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A B S T R A C T The circulatory effects of selective metabolic inhibition of glycolysis and of the tricarboxylic acid cycle by iodoacetate and fluoroacetate were studied in intact chloralose-anesthetized dogs. Pulmonary arterial blood pressure and vascular resistance increased after administration of both inhibitors, but neither systemic hemodynamics nor myocardial contractility changed significantly. Coronary blood flow did not change after iodoacetate administration but increased four-to fivefold after fluoroacetate. Administration of normal saline had no effect on any of the parameters. The changes in pulmonary arterial blood pressure and coronary blood flow after fluoroacetate were not mediated via the autonomic nerves or adrenergic neurohumors because they still occurred after autonomic nervous system inhibition. Neither myocardial oxygen consumption nor left ventricular work changed. A selective increase in myocardial blood flow also occurred in conscious dogs after fluoroacetate administration; hepatic artery flow was reduced, but other organ flows did not change significantly. These results indicate that pulmonary pressor and coronary dilator effects may be produced in intact dogs by selective metabolic blockade, in the absence of reduced oxygen supply or impairment in the electron transport system. These results also suggest that the increases in pulmonary arterial blood pressure, coronary blood flow, and cardiac output that occur during hypoxia probably are related to separate metabolic events in the tissue.

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“…This highly conserved physiological response requires oxygen and pH sensing coupled with vasodilation. While this process was first characterized more than 80 years ago (1,2), the precise identity and mechanism of the oxygen sensor and mediators of vasodilation remain unknown (3,4). From an oxygen-sensing standpoint, a situation in which the metabolic demand of a tissue exceeds oxygen delivery causes a divergence from the normal relationship between tissue oxygen consumption and vascular oxygen delivery.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control

Huang¹

2005

Journal of Clinical Investigation

471

511

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Hypoxic vasodilation is a fundamental, highly conserved physiological response that requires oxygen and/or pH sensing coupled to vasodilation. While this process was first characterized more than 80 years ago, the precise identity and mechanism of the oxygen sensor and mediators of vasodilation remain uncertain. In support of a possible role for hemoglobin (Hb) as a sensor and effector of hypoxic vasodilation, here we show biochemical evidence that Hb exhibits enzymatic behavior as a nitrite reductase, with maximal NO generation rates occurring near the oxy-to-deoxy (R-to-T) allosteric structural transition of the protein. The observed rate of nitrite reduction by Hb deviates from second-order kinetics, and sigmoidal reaction progress is determined by a balance between 2 opposing chemistries of the heme in the R (oxygenated conformation) and T (deoxygenated conformation) allosteric quaternary structures of the Hb tetramer -the greater reductive potential of deoxyheme in the R state tetramer and the number of unligated deoxyheme sites necessary for nitrite binding, which are more plentiful in the T state tetramer. These opposing chemistries result in a maximal nitrite reduction rate when Hb is 40-60% saturated with oxygen (near the Hb P 50 ), an apparent ideal set point for hypoxiaresponsive NO generation. These data suggest that the oxygen sensor for hypoxic vasodilation is determined by Hb oxygen saturation and quaternary structure and that the nitrite reductase activity of Hb generates NO gas under allosteric and pH control.

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The influence of chemical factors on the coronary circulation

Cited by 177 publications

References 7 publications

Release of adenosine triphosphate from isolated adult heart cells in response to hypoxia

Release of adenosine triphosphate from isolated adult heart cells in response to hypoxia

Metabolic control of circulation. Effects of iodoacetate and fluoroacetate.

Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control

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