A pharmacological analysis of the possible role of vasoactive mediators in compensatory coronary blood flow

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Abstract

Background: Coronary blood flow in one (circumflex) branch of the left coronary artery increases when an adjacent (left anterior descending [LAD]) branch is occluded for periods of between 1 min and 25 min. Objective: To examine the possible role of the myocardial release of vasoactive substances in such 'compensatory blood flow' increase by the classical pharmacological approach of inhibition of synthesis, or blockade at the receptor level, of the most likely mediators. Methods: In pentobarbitone anesthetized, thoracotomized dogs, coronary blood flow changes were measured in both the LAD (using a Doppler flow probe) and the left circumflex (using an electromagnetic flow probe) coronary arteries. Results: The flow increase during 5 min occlusions of the LAD coronary artery was unaffected by blockade of adenosine receptors by 8-sulfophenyltheophylline, inhibition of prostanoid synthesis by sodium meclofenamate or celecoxib, blockade of bradykinin B1 receptors by icatibant, inhibition of nitric oxide synthesis by Nω-nitro-L-arginine methyl ester (L-NAME), inhibition of guanylyl cyclase by methylene blue, or opening (using diazoxide) and closing (using glibenclamide or 5-hydroxydecanote) of ATP-dependent K+ channels. Neither dual blockade with L-NAME and glibenclamide, or meclofenamate and 5-hydroxydecanote, nor triple blockade with L-NAME, glibenclamide and 8-sulfophenyltheophylline, modified the blood flow response. However, it was greatly reduced (60%) by metoprolol. Conclusions: These results suggest that coronary vascular beta1-adrenoceptors are involved in 'compensatory' vasodilation, whereas bradykinin, nitric oxide, prostanoids and ATP-dependent K+ channels are seemingly not required for this flow increase.

Original languageEnglish
Pages (from-to)7-14
Number of pages8
JournalExperimental and Clinical Cardiology
Volume13
Issue number1
Publication statusPublished - 2008

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Glyburide
NG-Nitroarginine Methyl Ester
Meclofenamic Acid
Pharmacology
Coronary Vessels
Celecoxib
Prostaglandins
Nitric Oxide
Bradykinin B1 Receptors
Adenosine Triphosphate
Diazoxide
Purinergic P1 Receptors
Metoprolol
Guanylate Cyclase
Methylene Blue
Electromagnetic Phenomena
Bradykinin
Pentobarbital
Vasodilation
Adrenergic Receptors

Keywords

  • Coronary blood flow
  • Myocardial ischemia
  • Vasoactive substances

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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title = "A pharmacological analysis of the possible role of vasoactive mediators in compensatory coronary blood flow",
abstract = "Background: Coronary blood flow in one (circumflex) branch of the left coronary artery increases when an adjacent (left anterior descending [LAD]) branch is occluded for periods of between 1 min and 25 min. Objective: To examine the possible role of the myocardial release of vasoactive substances in such 'compensatory blood flow' increase by the classical pharmacological approach of inhibition of synthesis, or blockade at the receptor level, of the most likely mediators. Methods: In pentobarbitone anesthetized, thoracotomized dogs, coronary blood flow changes were measured in both the LAD (using a Doppler flow probe) and the left circumflex (using an electromagnetic flow probe) coronary arteries. Results: The flow increase during 5 min occlusions of the LAD coronary artery was unaffected by blockade of adenosine receptors by 8-sulfophenyltheophylline, inhibition of prostanoid synthesis by sodium meclofenamate or celecoxib, blockade of bradykinin B1 receptors by icatibant, inhibition of nitric oxide synthesis by Nω-nitro-L-arginine methyl ester (L-NAME), inhibition of guanylyl cyclase by methylene blue, or opening (using diazoxide) and closing (using glibenclamide or 5-hydroxydecanote) of ATP-dependent K+ channels. Neither dual blockade with L-NAME and glibenclamide, or meclofenamate and 5-hydroxydecanote, nor triple blockade with L-NAME, glibenclamide and 8-sulfophenyltheophylline, modified the blood flow response. However, it was greatly reduced (60{\%}) by metoprolol. Conclusions: These results suggest that coronary vascular beta1-adrenoceptors are involved in 'compensatory' vasodilation, whereas bradykinin, nitric oxide, prostanoids and ATP-dependent K+ channels are seemingly not required for this flow increase.",
keywords = "Coronary blood flow, Myocardial ischemia, Vasoactive substances",
author = "J. Parratt and A. V{\'e}gh",
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language = "English",
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N2 - Background: Coronary blood flow in one (circumflex) branch of the left coronary artery increases when an adjacent (left anterior descending [LAD]) branch is occluded for periods of between 1 min and 25 min. Objective: To examine the possible role of the myocardial release of vasoactive substances in such 'compensatory blood flow' increase by the classical pharmacological approach of inhibition of synthesis, or blockade at the receptor level, of the most likely mediators. Methods: In pentobarbitone anesthetized, thoracotomized dogs, coronary blood flow changes were measured in both the LAD (using a Doppler flow probe) and the left circumflex (using an electromagnetic flow probe) coronary arteries. Results: The flow increase during 5 min occlusions of the LAD coronary artery was unaffected by blockade of adenosine receptors by 8-sulfophenyltheophylline, inhibition of prostanoid synthesis by sodium meclofenamate or celecoxib, blockade of bradykinin B1 receptors by icatibant, inhibition of nitric oxide synthesis by Nω-nitro-L-arginine methyl ester (L-NAME), inhibition of guanylyl cyclase by methylene blue, or opening (using diazoxide) and closing (using glibenclamide or 5-hydroxydecanote) of ATP-dependent K+ channels. Neither dual blockade with L-NAME and glibenclamide, or meclofenamate and 5-hydroxydecanote, nor triple blockade with L-NAME, glibenclamide and 8-sulfophenyltheophylline, modified the blood flow response. However, it was greatly reduced (60%) by metoprolol. Conclusions: These results suggest that coronary vascular beta1-adrenoceptors are involved in 'compensatory' vasodilation, whereas bradykinin, nitric oxide, prostanoids and ATP-dependent K+ channels are seemingly not required for this flow increase.

AB - Background: Coronary blood flow in one (circumflex) branch of the left coronary artery increases when an adjacent (left anterior descending [LAD]) branch is occluded for periods of between 1 min and 25 min. Objective: To examine the possible role of the myocardial release of vasoactive substances in such 'compensatory blood flow' increase by the classical pharmacological approach of inhibition of synthesis, or blockade at the receptor level, of the most likely mediators. Methods: In pentobarbitone anesthetized, thoracotomized dogs, coronary blood flow changes were measured in both the LAD (using a Doppler flow probe) and the left circumflex (using an electromagnetic flow probe) coronary arteries. Results: The flow increase during 5 min occlusions of the LAD coronary artery was unaffected by blockade of adenosine receptors by 8-sulfophenyltheophylline, inhibition of prostanoid synthesis by sodium meclofenamate or celecoxib, blockade of bradykinin B1 receptors by icatibant, inhibition of nitric oxide synthesis by Nω-nitro-L-arginine methyl ester (L-NAME), inhibition of guanylyl cyclase by methylene blue, or opening (using diazoxide) and closing (using glibenclamide or 5-hydroxydecanote) of ATP-dependent K+ channels. Neither dual blockade with L-NAME and glibenclamide, or meclofenamate and 5-hydroxydecanote, nor triple blockade with L-NAME, glibenclamide and 8-sulfophenyltheophylline, modified the blood flow response. However, it was greatly reduced (60%) by metoprolol. Conclusions: These results suggest that coronary vascular beta1-adrenoceptors are involved in 'compensatory' vasodilation, whereas bradykinin, nitric oxide, prostanoids and ATP-dependent K+ channels are seemingly not required for this flow increase.

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