title: Both beta1- and beta2-adrenoceptors contribute to feedforward coronary resistance vessel dilation during exercise.
abstract: During exercise, beta-feedforward coronary vasodilation has been shown to contribute to the matching of myocardial oxygen supply with the demand of the myocardium. Since both beta(1)- and beta(2)-adrenoceptors are present in the coronary microvasculature, we investigated the relative contribution of these subtypes to beta-feedforward coronary vasodilation during exercise as well as to infusion of the beta(1)-agonist norepinephrine and the beta(1)- and beta(2)-agonist isoproterenol. Chronically instrumented swine were studied at rest and during graded treadmill exercise (1-5 km/h) under control conditions and after beta(1)-blockade with metoprolol (0.5 mg/kg iv) and beta(1)/beta(2)-blockade with propranolol (0.5 mg/kg iv). The selectivity and degree of beta-blockade of metoprolol and propranolol were confirmed using isoproterenol infusion (0.05-0.4 microg. kg(-1).min(-1)) under resting conditions. Isoproterenol-induced coronary vasodilation was mediated through the beta(2)-adrenoceptor, whereas norepinephrine-induced coronary vasodilation was principally mediated through the beta(1)-adrenoceptor. Exercise resulted in a significant increase in left ventricular norepinephrine release and epinephrine uptake. beta(1)-Adrenoceptor blockade with metoprolol had very little effect under resting conditions. However, during exercise, metoprolol attenuated the increase in myocardial oxygen supply in excess of the reduction in myocardial oxygen demand, as evidenced by a progressive decrease in coronary venous Po(2). Consequently, metoprolol caused a clockwise rotation of the relationship between myocardial oxygen consumption and coronary venous Po(2). Additional beta(2)-adrenoceptor blockade with propranolol further inhibited myocardial oxygen supply during exercise, resulting in a further clockwise rotation of the relationship between myocardial oxygen consumption and coronary venous Po(2). In conclusion, both beta(1)- and beta(2)-adrenoceptors contribute to the beta-feedforward coronary resistance vessel dilation during exercise.
authors.affiliation: Dept. of Cardiology, Univ. Medical Center Rotterdam, The Netherlands.
authors.forename: Fen
authors.initials: F
authors.lastname: Gao
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: de Beer
authors.forename: Maaike
authors.initials: M
authors.lastname: Hoekstra
authors.forename: Chuanshi
authors.initials: C
authors.lastname: Xiao
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
authors.forename: Daphne
authors.initials: D
authors.lastname: Merkus
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D008790:Metoprolol; D007545:Isoproterenol; D010100:Oxygen; D009638:Norepinephrine