Plasma ATP during exercise: possible role in regulation of coronary blood flow

It was previously shown that red blood cells release ATP when blood oxygen tension decreases. ATP acts on microvascular endothelial cells to produce a retrograde conducted vasodilation (presumably via gap junctions) to the upstream arteriole. These observations form the basis for an ATP hypothesis of local metabolic control of coronary blood flow due to vasodilation in microvascular units where myocardial oxygen extraction is high. Dogs ( n = 10) were instrumented with catheters in the aorta and coronary sinus, and a flow transducer was placed around the circumflex coronary artery. Arterial and coronary venous plasma ATP concentrations were measured at rest and during three levels of treadmill exercise by using a luciferin-luciferase assay. During exercise, myocardial oxygen consumption increased ∼3.2-fold, coronary blood flow increased ∼2.7-fold, and coronary venous oxygen tension decreased from 19 to 12.9 mmHg. Coronary venous plasma ATP concentration increased significantly from 31.1 to 51.2 nM ( P < 0.01) during exercise. Coronary blood flow increased linearly with coronary venous ATP concentration ( P < 0.01). Coronary venous-arterial plasma ATP concentration difference increased significantly during exercise ( P < 0.05). The data support the hypothesis that ATP is one of the factors controlling coronary blood flow during exercise.

Selective blockade of mitochondrial KATPchannels does not impair myocardial oxygen consumption

Opening of mitochondrial ATP-sensitive potassium (KATP) channels has been postulated to prevent inhibition of respiration resulting from matrix contraction during high rates of ATP synthesis. Glibenclamide, which blocks KATP channels on the sarcolemma of vascular smooth muscle cells and myocardial myocytes as well as on the inner mitochondrial membrane, results in a decrease of myocardial oxygen consumption (MV˙o 2) both at rest and during exercise. This study examined whether this represents a primary effect of blockade of mitochondrial KATP channels or occurs secondary to coronary resistance vessel constriction with a decrease of coronary blood flow (CBF) and myocardial oxygen availability. MV˙o 2 was measured at rest and during treadmill exercise in 10 dogs during control conditions, after selective mitochondrial KATP channel blockade with 5-hydroxydecanoate (5-HD), and after nonselective KATPchannel blockade with glibenclamide. During control conditions, exercise resulted in progressive increases of CBF and MV˙o 2. Glibenclamide (50 μg · kg−1 · min−1 ic) resulted in a 17 ± 6% decrease of resting CBF with a downward shift of CBF during exercise and a decrease of coronary venous Po 2, indicating increased myocardial oxygen extraction. In contrast with the effects of glibenclamide, 5-HD (0.7 mg · kg−1 · min−1 ic) had no effect on CBF, MV˙o 2, or myocardial oxygen extraction. These findings suggest that glibenclamide decreased MV˙o 2 by causing resistance vessel constriction with a decrease of CBF and oxygen available to the myocardium rather than to a primary reduction of mitochondrial respiration.