Role of K+ ATP channels and adenosine in the regulation of coronary blood flow during exercise with normal and restricted coronary blood flow.

Abstract

Regulation of coronary vasomotor tone during exercise is incompletely understood. We investigated the contributions of K ϩ ATP channels and adenosine to the coronary vasodilation that occurs during exercise in the normal heart and in the presence of a coronary artery stenosis. Dogs that were chronically instrumented with a Doppler flow probe, hydraulic occluder, and indwelling catheter on the left anterior descending coronary artery were exercised on a treadmill to produce heart rates of ‫ف‬ 200 beats/min. By graded inflation of the occluder to produce a wide range of coronary stenosis severities, we determined the coronary pressure-flow relation. K

Role of A2A‐adenosine receptor activation for ATP‐mediated coronary vasodilation in guinea‐pig isolated heart

“…Adenosine causes coronary vasodilation either when administered exogenously or when formed endogenously during metabolic stress (Berne, 1963;Olsson & Pearson, 1990;Duncker et al, 1996;Stepp et al, 1996). In the heart, adenosine reduces oxygen demand by a negative inotropic and chronotropic as well as an anti-b-adrenergic e ect, and increases oxygen supply by its action as a coronary vasodilator.…”

ATP-Dependent K+ Channels Contribute to Local Metabolic Coronary Vasodilation in Experimental Diabetes

“…The experimental protocol described above was repeated in the diabetic animals at least 7 days after the alloxan injection with and without glibenclamide. In addition, three experiments were also conducted at rest and during exercise with glibenclamide in nondiabetic dogs to confirm the previous findings that K ATP channels are not required for exercise-induced coronary vasodilation (3)(4)(5)7,8). Assessing the relationship between coronary blood flow and myocardial metabolism.…”

“…These studies indicate that K ATP channels are important in regulating coronary vascular resistance under baseline conditions (3-10), during hypoxic coronary vasodilation (11,12), and during reactive coronary hyperemia (1,4,13). However, it does not appear that K ATP channels are required to increase coronary blood flow when myocardial metabolism is increased (3)(4)(5)7,8).Recently, Kersten et al (14) found that diabetes enhanced K ATP channel-mediated coronary vasodilation of coronary arterioles, suggesting that K ATP channels are important in local metabolic coronary vasodilation in diabetes. Supporting this notion are the results of Shimoni et al (15) showing that the half-maximal inhibitory concentration (IC 50 ) for ATP-dependent inhibition of K ATP channels was approximately twofold higher for channels from diabetic rat hearts.…”

“…These studies indicate that K ATP channels are important in regulating coronary vascular resistance under baseline conditions (3-10), during hypoxic coronary vasodilation (11,12), and during reactive coronary hyperemia (1,4,13). However, it does not appear that K ATP channels are required to increase coronary blood flow when myocardial metabolism is increased (3)(4)(5)7,8).…”

“…umerous investigations have focused on the role of ATP-dependent K ϩ (K ATP ) channels in coronary blood flow regulation (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). These studies indicate that K ATP channels are important in regulating coronary vascular resistance under baseline conditions (3)(4)(5)(6)(7)(8)(9)(10), during hypoxic coronary vasodilation (11,12), and during reactive coronary hyperemia (1,4,13).…”