Abstract des Autors

Recent experiments demonstrate that feedforward sympathetic beta-adrenoceptor coronary vasodilation occurs during exercise. The present study quantitatively examined the contributions of epinephrine and norepinephrine to exercise coronary hyperemia and tested the hypothesis that circulating epinephrine causes feedforward beta-receptor-mediated coronary dilation. Dogs (n=10) were chronically instrumented with a circumflex coronary artery flow transducer and catheters in the aorta and coronary sinus. During strenuous treadmill exercise, myocardial oxygen consumption increased by ca. 3.9-fold, coronary blood flow increased by ca. 3.6-fold, and arterial plasma epinephrine concentration increased by ca. 2.4-fold over resting levels. At arterial concentrations matching those during strenuous exercise, epinephrine infused at rest (n=6) produced modest increases (18%) in flow and myocardial oxygen consumption but no evidence of direct beta-adrenoceptor-mediated coronary vasodilation. Arterial norepinephrine concentration increased by ca. 5.4-fold during exercise, and coronary venous norepinephrine was always higher than arterial, indicating norepinephrine release from cardiac sympathetic nerves. With the use of a mathematical model of cardiac capillary norepinephrine transport, these norepinephrine concentrations predict an average interstitial norepinephrine concentration of ca. 12 nM during strenuous exercise. Published dose-response data indicate that this norepinephrine concentration increases isolated coronary arteriolar conductance by ca. 67%, which can account for ca. 25% of the increase in flow observed during exercise. It is concluded that a significant portion of coronary exercise hyperemia (ca. 25%) can be accounted for by direct feedforward beta-adrenoceptor coronary vascular effects of norepinephrine, with little effect from circulating epinephrine. Verf.-Referat