Role of KATP 1 channels in regulation of systemic, pulmonary, and coronary vasomotor tone in exercising swine

Duncker, D. J., H. H. Oei, F. Hu, R. Stubenitsky, and P. D. Verdouw. Role of KATP 1 channels in regulation of systemic, pulmonary, and coronary vasomotor tone in exercising swine. Am J Physiol Heart Circ Physiol 280: H22–H33, 2001.—The role of ATP-sensitive K (KATP 1 ) channels in vasomotor tone regulation during metabolic stimulation is incompletely understood. Consequently, we studied the contribution of KATP 1 channels to vasomotor tone regulation in the systemic, pulmonary, and coronary vascular bed in nine treadmill-exercising swine. Exercise up to 85% of maximum heart rate increased body O2 consumption fourfold, accommodated by a doubling of both cardiac output and body O2 extraction. Mean aortic pressure was unchanged, implying that systemic vascular conductance (SVC) also doubled, whereas pulmonary artery pressure increased almost in parallel with cardiac output, so that pulmonary vascular conductance (PVC) increased only 25 6 9% (both P , 0.05). Myocardial O2 consumption tripled during exercise, which was paralleled by an equivalent increase in O2 supply so that coronary venous PO2 was maintained. Selective KATP 1 channel blockade with glibenclamide (3 mg/kg iv), decreased SVC by 29 6 4% at rest and by 10 6 2% at 5 km/h (both P , 0.05), whereas PVC was unchanged. Glibenclamide decreased coronary vascular conductance and hence myocardial O2 delivery, necessitating an increase in O2 extraction from 76 6 2% to 86 6 2% at rest and from 79 6 2% to 83 6 1% at 5 km/h. Consequently, coronary venous PO2 decreased from 25 6 1 to 17 6 1 mmHg at rest and from 23 6 1 to 20 6 1 mmHg at 5 km/h (all values are P , 0.05). In conclusion, KATP 1 channels dilate the systemic and coronary, but not the pulmonary, resistance vessels at rest and during exercise in swine. However, opening of KATP 1 channels is not mandatory for the exercise-induced systemic and coronary vasodilation.