Influence of alpha-adrenergic blockade on platelet-mediated thrombosis in stenosed canine coronary arteries.
The functional significance of platelet alpha-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 reduction 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 alpha-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 alpha 1-blocker, 2 mg . kg-1, n = 8), yohimbine (an alpha 2-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 alpha-blocking action equivalent to or greater than that of phentolamine (alpha-agonist dose-response studies).(ABSTRACT TRUNCATED AT 250 WORDS)
Bolli
R
R
Brandon
T A
TA
Mace
M L
ML
Weibaecher
D G
DG
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity; D001792:Blood Platelets / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000494:pharmacology; D010974:Platelet Aggregation; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine; D010646:Phentolamine