Role of K(ATP)/+ channels and adenosine in the control of coronary blood flow during exercise

Keith Neu Richmond, Johnathan D. Tune, Mark W. Gorman, Eric O. Feigl

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The present study was designed to examine the role of ATP-sensitive potassium K(ATP)/+ channels during exercise and to test the hypothesis that adenosine increases to compensate for the loss of K(ATP)/+ channel function and adenosine inhibition produced by glibenclamide. Graded treadmill exercise was used to increase myocardial O2 consumption in dogs before and during K(ATP)/+ channel blockade with glibenclamide (1 mg/kg iv), which also blocks adenosine mediated coronary vasodilation. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous values by using a previously tested mathematical model (Kroll K and Stepp DW. Am J Physiol Heart Circ Physiol 270: H1469-H1483, 1996). Coronary venous O2 tension was used as an index of the balance between O2 delivery and myocardial O2 consumption. During control exercise, myocardial O2 consumption increased ~4-fold, and coronary venous O2 tension fell from 19 to 14 Torr. After K(ATP)/+ channel blockade, coronary venous O2 tension was decreased below control vehicle values at rest and during exercise. However, during exercise with glibenclamide, the slope of the line of coronary venous O2 tension vs. myocardial O2 consumption was the same as during control exercise. Estimated interstitial adenosine concentration with glibenclamide was not different from control vehicle and was well below the level necessary to overcome the 10-fold shift in the adenosine dose-response curve due to glibenclamide. In conclusion, K(ATP)/+ channel blockade decreases the balance between resting coronary O2 delivery and myocardial O2 consumption, but K(ATP)/+ channels are not required for the increase in coronary blood flow during exercise. Furthermore, interstitial adenosine concentration does not increase to compensate for the loss of K(ATP)/+ channel function.

Original languageEnglish
Pages (from-to)529-536
Number of pages8
JournalJournal of Applied Physiology
Volume89
Issue number2
DOIs
StatePublished - 2000

Keywords

  • ATP-sensitive potassium channels
  • Canine
  • Glibenclamide

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