Integrated control of coronary blood flow in exercising swine by adenosine, nitric oxide, and K-ATP channels

Duncker, Dirk J.; Sorop, Oana; Wouw, Jens van de; Fen, Gao; Beer, Vincent J. de; Taverne, Yannick J.; Graaff, Henri J. D. de und Merkus, Daphne (2022): Integrated control of coronary blood flow in exercising swine by adenosine, nitric oxide, and K-ATP channels. In: American Journal of Physiology: Heart and Circulatory Physiology, Bd. 323, Nr. 6: H1080-H1090

Abstract

The interplay of mechanisms regulating coronary blood flow (CBF) remains incompletely understood. Previous studies in dogs indicated that CBF regulation by K-ATP channels, adenosine, and nitric oxide (NO) follows a nonlinear redundancy design and fully accounted for exercise-induced coronary vasodilation. Conversely, in swine, these mechanisms appear to regulate CBF in a linear additive fashion with considerable exercise-induced vasodilation remaining when all three mechanisms are inhibited. A direct comparison between these studies is hampered by the different doses and administration routes (intravenous vs. intracoronary) of drugs inhibiting these mechanisms. Here, we investigated the role of K-ATP channels, adenosine, and NO in CBF regulation in swine using identical drug regimen as previously employed in dogs. Instrumented swine were exercised on a motor-driven treadmill, before and after blockade of K-ATP channels (glibenclamide, 50 mu g/kg/min ic) and combination of inhibition of NO synthase (N-omega-nitro-L-arginine, NLA, 1.5 mg/kg ic) and adenosine receptors (8-phenyltheophylline, 8PT, 5 mg/kg iv) or their combination NLA + 8PT + glibenclamide. Glibenclamide and NLA + 8PT each produced coronary vasoconstriction both at rest and during exercise, whereas the combination of NLA + 8PT + glibenclamide resulted in a small further coronary vasoconstriction compared with NLA + 8PT that was, however, less than the sum of the vasoconstriction produced by NLA + 8PT and glibenclamide, each. Thus, in contrast to previous observations in the dog, 1) the coronary vasoconstrictor effect of glibenclamide was not enhanced in the presence of NLA + 8PT and 2) the exercise-induced increase in CBF was largely maintained. These findings show profound species differences in the mechanisms controlling CBF at rest and during exercise. NEW & NOTEWORTHY The present study demonstrates important species differences in the regulation of coronary blood flow by adenosine, NO, and K-ATP channels at rest and during exercise. In swine, these mechanisms follow a linear additive design, as opposed to dogs which follow a nonlinear redundant design. Simultaneous blockade of all three mechanisms virtually abolished exercise-induced coronary vasodilation in dogs, whereas a substantial vasodilator reserve could still be recruited during exercise in swine.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0363-6135
• Sprache: Englisch