Demonstration of specific dopamine-1 receptor-mediated coronary vasodilation in the anesthetized dog.
This study was conducted to identify the vascular dopamine receptor subtype responsible for specific dopamine-mediated coronary vasodilation. The left circumflex coronary artery (LCX) of pentobarbital anesthetized, open chest dogs was isolated and perfused under either constant flow or constant pressure conditions with blood withdrawn from a cannulated left femoral artery. In animals subjected to constant flow LCX perfusion, after beta adrenoceptor blockade with nadolol (4 mg/kg), alpha-1 adrenoceptor blockade with prazosin (0.5 mg/kg) and alpha-2 adrenoceptor blockade with idazoxan (1.0 mg/kg), intracoronary (c) injection of dopamine (0.01-10 micrograms/kg) produced a dose-dependent decrease in LCX perfusion pressure which was unaltered by administration of the dopamine-2 receptor antagonist domperidone (10 micrograms/kg) but which was blocked completely by the dopamine-1 receptor antagonist SK&F R-83566 (5 micrograms/kg). Similarly, under conditions of constant pressure LCX perfusion and after combined beta, alpha-1 and alpha-2 adrenoceptor blockade, i.c. administration of dopamine produced a dose-related increase in LCX coronary blood flow which was inhibited by SK&F R-83566 but not by domperidone. Direct i.c. administration of the selective dopamine-1 receptor agonist, fenoldopam (1 microgram/kg), resulted in an increase in LCX coronary blood flow which was eliminated completely after administration of SK&F R-83566. Doses of the selective dopamine-2 receptor agonist, dipropyldopamine (0.1-30 micrograms/kg), effective in producing blood flow increases in the femoral vascular bed and which could be antagonized by domperidone, produced only minimal and inconsistent changes in LCX coronary blood flow. Our data demonstrate that direct, dopamine-mediated coronary vasodilation in vivo occurs via stimulation of a vascular receptor of the dopamine-1 subtype.
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Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, Pennsylvania.
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives*; D000758:Anesthesia; D000787:Angina Pectoris / Q000188:drug therapy; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D018818:Fenoldopam; D008297:Male; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D014664:Vasodilation / Q000187:drug effects*
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001552:Benzazepines; D004294:Domperidone; D004298:Dopamine; D018818:Fenoldopam; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; C044846:SKF83566