Alpha 1 and alpha 2-adrenergic control of large and small coronary arteries during exercise in conscious dogs under beta-blockade.
The aim of this study was to determine the relative roles of alpha 1-and alpha 2-adrenoceptors at the level of large epicardial and small resistance coronary arteries when sympathetic tone is increased by exercise in conscious dogs. The responses of left circumflex coronary artery diameter and blood flow were investigated at rest and during graded treadmill exercise (5, 10 and 12 km/h) in six chronically instrumented dogs during control conditions (saline) and after administration of propranolol (1 mg/kg) either alone or in combination with either prazosin (50 micrograms/kg), or idazoxan (300 micrograms/kg), or the association of prazosin+idazoxan (same doses). In control conditions, graded treadmill exercise resulted in a progressive increase in coronary artery diameter (+3.8 +/- 0.6% from 3479 +/- 80 microns) and in a decrease in coronary vascular resistance (-46.0 +/- 4.5% from 8.49 +/- 1.51 mmHg/cm/s). Propranolol significantly constricted large (-4.4 +/- 0.6% from 3486 +/- 87 microns) and limited dilation of small coronary arteries during exercise. These coronary effects of propranolol remained unchanged following additional alpha 2-adrenoceptor blockade by idazoxan but were abolished following alpha 1-adrenoceptor blockade by prazosin, given either alone or combined with idazoxan. Thus, alpha 1- but not alpha 2-adrenoceptors are responsible for propranolol-induced constriction of large coronary arteries and limitation of small coronary arteries dilation during exercise in conscious dogs.
Vigue
B
B
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, France.
Ghaleh
B
B
Giudicelli
J F
JF
Berdeaux
A
A
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D003331:Coronary Vessels / Q000187:drug effects* / Q000648:ultrastructure*; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D019329:Idazoxan; D005082:Physical Exertion / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D004146:Dioxanes; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011433:Propranolol; D011224:Prazosin; D019329:Idazoxan