Opposed responses of large and small coronary arteries to propranolol during exercise in dogs.
This study was carried out to determine the relative role of alpha- and beta-adrenoceptors at the level of large epicardial and small resistance coronary arteries when sympathetic tone is increased by exercise. The responses of left circumflex coronary diameter and blood flow were examined at rest and during treadmill exercise in seven chronically instrumented dogs during control conditions (saline) and after propranolol administration (1 mg/kg) either alone or in combination with phentolamine (1.5 mg/kg). In control conditions, graded treadmill exercise (5, 10, and 12 km/h) resulted in a progressive increase in coronary artery diameter and decrease in coronary vascular resistance. After propranolol, coronary vascular resistance slightly increased at rest and then progressively decreased during exercise. Surprisingly, coronary artery diameter significantly decreased at rest as well as throughout the exercise period. Phentolamine significantly reduced the propranolol-induced effects on coronary arterial diameter but did not restore the exercise-induced dilation of the large coronary arteries observed during control conditions. In addition, phentolamine prevented the propranolol-induced increase in coronary vascular resistance at rest and reinforced the exercise-induced decrease in coronary vascular resistance observed under propranolol. Thus beta-adrenoceptors are essential in the mediation of exercise-induced dilation of large coronary arteries. In contrast, activation of beta-adrenoceptors is only partially responsible for the decrease in coronary vascular resistance during exercise. Finally, constriction of large coronary arteries after propranolol is mainly explained by the unmasking of alpha-adrenergic tone at rest, but other mechanisms are involved during exercise.
Berdeaux
A
A
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
Drieu la Rochelle
C
C
Richard
V
V
Giudicelli
J F
JF
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004338:Drug Combinations; D006439:Hemodynamics / Q000187:drug effects; D009043:Motor Activity / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D004338:Drug Combinations; D012965:Sodium Chloride; D011433:Propranolol; D010646:Phentolamine