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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/H2075    most recent 01109.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Merkus, D. Articles by Duncker, D. J. Search for Related Content PubMed PubMed Citation Articles by Merkus, D. Articles by Duncker, D. J.

NO and prostanoids blunt endothelin-mediated coronary vasoconstrictor influence in exercising swine

¹Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, and ²Department of Internal Medicine, Cardiovascular Research School COEUR, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands

Submitted 20 October 2005 ; accepted in final form 1 June 2006

Withdrawal of the endothelin (ET)-mediated vasoconstrictor influence contributes to metabolic coronary vasodilation during exercise. Because production of nitric oxide (NO) and prostanoids increases with increasing shear stress and because NO and prostanoids are able to modify the release of ET, we hypothesized that the withdrawal of ET-mediated coronary vasoconstriction during exercise is mediated through NO and/or prostanoids. To test this hypothesis, 19 chronically instrumented swine were studied at rest and while running on a treadmill up to 85–90% of maximal heart rate. Blockade of ET_A/ET_B receptors with tezosentan resulted in an increase in coronary venous O₂ levels (i.e., in coronary vasodilation) at rest, which waned at increasing levels of exercise intensity. Inhibition of either NO synthase [N-nitro-L-arginine (L-NNA)] or cyclooxygenase (indomethacin) did not affect the response to tezosentan under resting conditions but unmasked a vasodilator response to tezosentan during exercise. The vasodilator response to tezosentan during exercise increased progressively after combined administration of L-NNA and indomethacin. These findings suggest that NO and prostanoids act synergistically to inhibit the vasoconstrictor influence of ET on the coronary circulation during exercise, thereby facilitating the exercise-induced vasodilation of coronary resistance vessels.

coronary circulation; coronary blood flow; myocardial oxygen balance; exercise

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