title: KCa+ channels contribute to exercise-induced coronary vasodilation in swine.
abstract: Coronary blood flow is controlled via several vasoactive mediators that exert their effect on coronary resistance vessel tone through activation of K(+) channels in vascular smooth muscle. Because Ca(2+)-activated K(+) (K(Ca)(+)) channels are the predominant K(+) channels in the coronary vasculature, we hypothesized that K(Ca)(+) channel activation contributes to exercise-induced coronary vasodilation. In view of previous observations that ATP-sensitive K(+) (K(ATP)(+)) channels contribute, in particular, to resting coronary resistance vessel tone, we additionally investigated the integrated control of coronary tone by K(Ca)(+) and K(ATP)(+) channels. For this purpose, the effect of K(Ca)(+) blockade with tetraethylammonium (TEA, 20 mg/kg iv) on coronary vasomotor tone was assessed in the absence and presence of K(ATP)(+) channel blockade with glibenclamide (3 mg/kg iv) in chronically instrumented swine at rest and during treadmill exercise. During exercise, myocardial O(2) delivery increased commensurately with the increase in myocardial O(2) consumption, so that myocardial O(2) extraction and coronary venous Po(2) (Pcv(O(2))) were maintained constant. TEA (in a dose that had no effect on K(ATP)(+) channels) had a small effect on the myocardial O(2) balance at rest and blunted the exercise-induced increase in myocardial O(2) delivery, resulting in a progressive decrease of Pcv(O(2)) with increasing exercise intensity. Conversely, at rest glibenclamide caused a marked decrease in Pcv(O(2)) that waned at higher exercise levels. Combined K(Ca)(+) and K(ATP)(+) channel blockade resulted in coronary vasoconstriction at rest that was similar to that caused by glibenclamide alone and that was maintained during exercise, suggesting that K(Ca)(+) and K(ATP)(+) channels act in a linear additive fashion. In conclusion, K(Ca)(+) channel activation contributes to the metabolic coronary vasodilation that occurs during exercise. Furthermore, in swine K(Ca)(+) and K(ATP)(+) channels contribute to coronary resistance vessel control in a linear additive fashion.
authors.affiliation: Experimental Cardiology, Thoraxcenter Erasmus MC, Univ. Medical Center Rotterdam, Box 1738, 3000DR Rotterdam, The Netherlands. d.merkus@erasmusmc.nl
authors.forename: Daphne
authors.initials: D
authors.lastname: Merkus
authors.forename: Oana
authors.initials: O
authors.lastname: Sorop
authors.forename: Birgit
authors.initials: B
authors.lastname: Houweling
authors.forename: Bas A
authors.initials: BA
authors.lastname: Hoogteijling
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D001784:Blood Gas Analysis; D003331:Coronary Vessels / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005080:Exercise Test; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010805:Physical Conditioning, Animal; D005082:Physical Exertion / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000819:agonists / Q000187:drug effects / Q000502:physiology*; D034421:Sus scrofa; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors; D014664:Vasodilation / Q000502:physiology*
chemical_list: D001578:Benzopyrans; D004095:Dihydropyridines; D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; C061050:bimakalim; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D005905:Glyburide