Enhanced coronary vasoconstrictor responses to 5-hydroxytryptamine in the presence of a coronary artery stenosis in anaesthetized dogs.
1. In the anaesthetized dog, left circumflex coronary artery blood flow and external diameter were measured and the vascular responses to an injection of 5-hydroxytryptamine (5-HT, 0.02-2 micrograms kg-1) assessed, before and after a screw clamp had been placed on the artery to produce a severe stenosis. 2. In the normal coronary circulation, intra-coronary (i.c.) injection of 5-HT increased coronary blood flow (CBF) but decreased the external diameter of the large coronary artery (CD), without affecting systemic mean arterial pressure or heart rate. 3. In the normal coronary circulation, the 5-HT-induced increases in CBF were unaffected by blockade of 5-HT2-receptors with ketanserin (0.1 mg kg-1 i.c.) but were significantly attenuated by blockade of 5-HT1-like receptors with methysergide (0.1 mg kg-1 i.c.). 4. In the presence of a severe stenosis, the increase in CBF produced by 5-HT was markedly attenuated and a secondary decrease in CBF was revealed. The stenosis also caused a marked enhancement of the 5-HT-induced constriction of the large artery, such that the reduction of the CD was approximately doubled at all doses of 5-HT tested. The enhanced 5-HT-induced reduction in CD was similar with placement of the stenosis either proximal or distal to the site of diameter measurement. 5. In the presence of the stenosis, blockade of 5-HT 2-receptors with ketanserin (0.1 mg kg-1 i.c.) significantly attenuated the 5-HT-induced decreases in CD and CBF. 6. These results demonstrate that, in the anaesthetized dog, placement of a severe, flow-limiting stenosis enhances 5-HT-induced constriction of the large coronary arteries and reveals a reduction in coronary blood flow. These observations support suggestions that, in the presence of coronary artery disease, 5-HT could contribute to reductions in coronary blood flow leading to myocardial ischaemia.
Woodman
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Department of Pharmacology, University of Melbourne, Parkville, Vic., Australia.
D000758:Anesthesia; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000033:anatomy & histology; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin; D008784:Methysergide