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

Research output: Contribution to journalArticle

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 - Mar 31 2008

Keywords

  • Coronary blood flow
  • Myocardial ischemia
  • Vasoactive substances

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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