title: Autonomic control of vasomotion in the porcine coronary circulation during treadmill exercise: evidence for feed-forward beta-adrenergic control.
abstract: To date, no studies have investigated coronary vasomotor control of myocardial O2 delivery (MDO2) and its modulation by the autonomic nervous system in the porcine heart during treadmill exercise. We studied 8 chronically instrumented swine under resting conditions and during graded treadmill exercise. Exercise up to 85% to 90% of maximum heart rate produced an increase in myocardial O2 consumption (MVO2) from 163+/-16 micromol/min (mean+/-SE) at rest to 423+/-75 micromol/min (P< or =0.05), which was paralleled by an increase in MDO2, so that myocardial O2 extraction (79+/-1% at rest) and coronary venous O2 tension (cvPO2, 23.7+/-1.0 mm Hg at rest) were maintained. Beta-adrenoceptor blockade blunted the exercise-induced increase of MDO2 out of proportion compared with the attenuation of the exercise-induced increase in MVO2, so that O2 extraction rose from 78+/-1% at rest to 83+/-1% during exercise and cvPO2 fell from 23.5+/-0.9 to 19.6+/-1.1 mm Hg (both P< or =0.05). In contrast, alpha-adrenoceptor blockade, either in the absence or presence of beta-adrenoceptor blockade, had no effect on myocardial O2 extraction or cvPO2 at rest or during exercise. Muscarinic receptor blockade resulted in a decreased O2 extraction and an increase in cvPO2 at rest, an effect that waned during exercise. The vasodilation produced by muscarinic receptor blockade was likely due to an increased beta-adrenoceptor activity, since combined muscarinic and beta-adrenoceptor blockade produced similar changes in O2 extraction and cvPO2, as did beta-adrenoceptor blockade alone. In conclusion, in swine myocardium, MVO2 and MDO2 are matched during exercise, which is the result of feed-forward beta-adrenergic vasodilation in conjunction with minimal a-adrenergic vasoconstriction. Beta-adrenergic vasodilation is due to an increase in sympathetic activity but may also be supported by withdrawal of muscarinic receptor-mediated inhibition of beta-adrenergic coronary vasodilation. The observation that cvPO2 levels are maintained even during heavy exercise suggests that a decrease in cvPO2 is not essential for coronary vasodilation during exercise.
authors.affiliation: Experimental Cardiology, Thoraxcenter, Cardiovascular Research Institute COEUR, Erasmus University Rotterdam, The Netherlands. Duncker@tch.fgg.eur.nl
authors.forename: D J
authors.initials: DJ
authors.lastname: Duncker
authors.forename: R
authors.initials: R
authors.lastname: Stubenitsky
authors.forename: P D
authors.initials: PD
authors.lastname: Verdouw
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D005080:Exercise Test; D006321:Heart / Q000502:physiology; D006439:Hemodynamics; D010101:Oxygen Consumption; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology; D013552:Swine; D014666:Vasomotor System / Q000502:physiology*
chemical_list: D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic