TY - JOUR
T1 - KATP+ channels, nitric oxide, and adenosine are not required for local metabolic coronary vasodilation
AU - Tune, Johnathan D.
AU - Richmond, Keith Neu
AU - Gorman, Mark W.
AU - Feigl, Eric O.
PY - 2001/2
Y1 - 2001/2
N2 - The role of ATP-sensitive K+ (KATP+) channels, nitric oxide, and adenosine in coronary exercise hyperemia was investigated. Dogs (n = 10) were chronically instrumented with catheters in the aorta and coronary sinus and instrumented with a flow transducer on the circumflex coronary artery. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous plasma concentrations using a previously tested mathematical model. Experiments were conducted at rest and during graded treadmill exercise with and without combined inhibition of KATP+ channels (glibenclamide, 1 mg/kg iv), nitric oxide synthesis (Nω-nitro-L-arginine, 35 mg/kg iv), and adenosine receptors (8-phenyltheophylline, 3 mg/kg iv). During control exercise, myocardial oxygen consumption increased ∼2.9-fold, coronary blood flow increased ∼2.6-fold, and coronary venous oxygen tension decreased from 19.9 ± 0.4 to 13.7 ± 0.6 mmHg. Triple blockade did not significantly change the myocardial oxygen consumption or coronary blood flow response during exercise but lowered the resting coronary venous oxygen tension to 10.0 ± 0.4 mmHg and during exercise to 6.2 ± 0.5 mmHg. Cardiac adenosine levels did not increase sufficiently to overcome the adenosine receptor blockade. These results indicate that combined inhibition of KATP+ channels, nitric oxide synthesis, and adenosine receptors lowers the balance between total oxygen supply and consumption at rest but that these factors are not required for local metabolic coronary vasodilation during exercise.
AB - The role of ATP-sensitive K+ (KATP+) channels, nitric oxide, and adenosine in coronary exercise hyperemia was investigated. Dogs (n = 10) were chronically instrumented with catheters in the aorta and coronary sinus and instrumented with a flow transducer on the circumflex coronary artery. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous plasma concentrations using a previously tested mathematical model. Experiments were conducted at rest and during graded treadmill exercise with and without combined inhibition of KATP+ channels (glibenclamide, 1 mg/kg iv), nitric oxide synthesis (Nω-nitro-L-arginine, 35 mg/kg iv), and adenosine receptors (8-phenyltheophylline, 3 mg/kg iv). During control exercise, myocardial oxygen consumption increased ∼2.9-fold, coronary blood flow increased ∼2.6-fold, and coronary venous oxygen tension decreased from 19.9 ± 0.4 to 13.7 ± 0.6 mmHg. Triple blockade did not significantly change the myocardial oxygen consumption or coronary blood flow response during exercise but lowered the resting coronary venous oxygen tension to 10.0 ± 0.4 mmHg and during exercise to 6.2 ± 0.5 mmHg. Cardiac adenosine levels did not increase sufficiently to overcome the adenosine receptor blockade. These results indicate that combined inhibition of KATP+ channels, nitric oxide synthesis, and adenosine receptors lowers the balance between total oxygen supply and consumption at rest but that these factors are not required for local metabolic coronary vasodilation during exercise.
KW - Coronary blood flow
KW - Exercise
KW - Myocardial oxygen consumption
UR - http://www.scopus.com/inward/record.url?scp=0034999434&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.2001.280.2.h868
DO - 10.1152/ajpheart.2001.280.2.h868
M3 - Article
C2 - 11158988
AN - SCOPUS:0034999434
SN - 0363-6135
VL - 280
SP - H868-H875
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 2 49-2
ER -