Effect of dopamine and blockade of dopaminergic and adrenergic receptors on coronary blood flow in ischemic rabbit myocardium.
The effect of a broad dose range of dopamine on coronary blood flow was studied in rabbits with coronary artery occlusion. Dopaminergic and adrenergic receptor blockade was established to distinguish the mechanism of the dopamine-induced increase in coronary blood flow. Dopamine, 10, 100, or 1,000 micrograms/kg/min, was infused in the presence of dopaminergic, beta-, or alpha-adrenergic receptor blockade. Coronary blood flow, as measured by radiolabeled microspheres, and hemodynamic parameters were monitored in 60 anesthetized open-chest rabbits. Dopamine, 1,000 micrograms/kg/min, significantly increased coronary blood flow 157% in normal and 118% in occluded rabbit myocardium. Propranolol (2 mg/kg) prevented the dopamine-induced increases in coronary blood flow within occluded and nonoccluded myocardium. Practolol (2 mg/kg) blunted the coronary blood flow increases within occluded myocardium, but flow within normal myocardium remained significantly elevated. In animals given phenoxybenzamine (2 mg/kg), dopamine infusion produced significant blood pressure reductions along with no change in either occluded or nonoccluded coronary blood flow. Bulbocapnine (8 mg/kg), a dopamine receptor antagonist, did not block blood flow increases in normal myocardium, but prevented significant increases in blood flow within occluded myocardium. It can be concluded that direct or indirect vasodilator receptors (dopaminergic, beta 1-, and beta 2-adrenoceptors) must be stimulated and perfusion pressure must not fall in order for dopamine to produce increases of coronary blood flow within occluded myocardium.
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D000818:Animals; D001060:Aporphines / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010643:Phenoxybenzamine / Q000494:pharmacology; D011217:Practolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*; D013565:Sympatholytics / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D001060:Aporphines; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D013565:Sympatholytics; D010643:Phenoxybenzamine; D011433:Propranolol; D011217:Practolol; D004298:Dopamine