Key result
In conscious dogs, alpha-1 but not alpha-2 adrenoceptors mediate propranolol-induced constriction of large coronary arteries (-4.4%) and limit small coronary artery dilation during exercise.
Why the study?
Does alpha-adrenoceptor blockade alter propranolol-induced coronary artery constriction during exercise in conscious dogs?
Does alpha-adrenoceptor blockade alter propranolol-induced coronary artery constriction during exercise in conscious dogs?
Absolute Event Rate: -4.4% vs 3.8%
Alpha 1-adrenoceptors, but not alpha 2-adrenoceptors, mediate propranolol-induced coronary artery constriction during exercise in conscious dogs.
Caution against extrapolating canine alpha-1 mediation to human beta-blocker therapy; leaves open translation of coronary vasoregulation mechanisms.
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.
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Vigué et al. (1993) studied this question. Propranolol alone or with prazosin and/or idazoxan vs. Saline (control) was evaluated on Change in large coronary artery diameter during exercise. In conscious dogs, alpha-1 but not alpha-2 adrenoceptors mediate propranolol-induced constriction of large coronary arteries (-4.4%) and limit small coronary artery dilation during exercise.
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