Influence of α-adrenergic blockade on platelet-mediated thrombosis in stenosed canine coronary arteries

Summary: The functional significance of platelet α-adrenergic receptors in vivo is uncertain. The aim of this study was to elucidate their role in experimental coronary thrombosis. In 46 open-chest dogs with a critical coronary stenosis produced by plicating the coronary artery wall with a suture, blood flow showed cyclical reductions followed by an abrupt return to control levels. The flow reductions were previously shown to be caused by platelet aggregation. In the present study they were unaffected by heparin (1,000 U·kg^-1·h^-1) at the start of the experiment but consistently abolished by aspirin (30 mg·kg^-1) at the end of the protocol, further supporting platelet aggregation as the primary mechanism.After 1 h of observation, dogs were assigned to one of the following groups: control (no intervention, n=9), phentolamine (a nonselective α-blocker) "low dose" (0.07 mg·kg^-1 bolus followed by 0.1 mg·kg^-1·min^-1, n=4), phentolamine "high dose" (3 mg·kg^-1 bolus followed by 0.07 mg·kg^-1·min^-1, n=6), prazosin (an α₁-blocker, 2 mg·kg^-1, n=8), yohimbine (an α₂-blocker, 3 mg·kg^-1, n= 11) or prazosin + yohimbine (same doses, n=8). In controls, cyclical reductions in flow continued unchanged for another hour. Phentolamine effected a partial dose-related inhibition of flow reductions; however, prazosin and yohimbine, given separately or in combination, failed to produce any significant effect despite an α-blocking action equivalent to or greater than that of phentolamine (α-agonist dose-response studies). Thus, α_1-, α_2- and combined α_1- and α₂-blockade, per se, did not interfere with coronary thrombosis in the face of elevated plasma levels of adrenaline and noradrenaline (285 ± 48 and 399 ± 31 ng·litre^-1, respectively). It is concluded that, in the dog, α-adrenoceptors do not contribute significantly to spontaneous formation of platelet coronary thrombi even at moderately increased levels of adrenergic stimulation. In addition, this study identifies an in vivo platelet-inhibitory activity of phentolamine that is independent of α-adrenergic blockade.