title: Modification of the ischaemic-induced contraction in the sheep circumflex coronary artery by various pharmacological antagonists.
abstract: 1. Sheep isolated circumflex coronary artery rings were exposed to simulated ischaemia (increased K+ reduced pH, hypoxia, reduced glucose and addition of lactate). Simulated ischaemia caused a transient relaxation lasting approximately 5 min followed by a sustained contraction that was reversible on washing with oxygenated Krebs solution. 2. Haemolysate caused a rise in baseline tension and augmented the ischaemic contraction. 3. The ischaemic contraction was abolished by BW 755C 5 microM and reduced by indomethacin 1 microM, quinacrine 50 microM or the thromboxane A2 antagonist BM 13177 10 microM. The leukotriene D4 antagonist, ICI 198615, had no effect. 4. The ischaemic-induced contraction was enhanced by propranolol 1 microM, methiothepin 1 microM and reduced by ketanserin 1 microM. 5. The ischaemic contraction was markedly inhibited by trypsin (1 mu ml-1) and by verapamil, cromakalim or sodium nitroprusside. 6. The following had no or little effect on the ischaemic contraction: Sar1-Thr8-angiotensin II, mepyramine, atropine, the spin trapping agent PBN or the free radical scavenger dimethylsulphoxide. Superoxide dismutase caused a slight enhancement. 7. The ischaemic-induced contraction was abolished by the simultaneous administration, at subthreshold concentrations, either of two vasodilators (iloprost and adenosine) or of a vasodilator and a vasoconstrictor (iloprost and U46619). 8. The ischaemic relaxation phase was reduced by propranolol and indomethacin, abolished by haemolysate and enhanced by quinacrine or cromakalim. 9. It is concluded that the ischaemic-induced contraction is caused by mediators released from the endothelium including a product of the lipoxygenase pathway. There is also evidence that simulated ischaemia causes the release of noradrenaline and 5-hydroxytryptamine.
authors.affiliation: Department of Physiology and Pharmacology, University of Strathclyde, Glasgow.
authors.forename: Y W
authors.initials: YW
authors.lastname: Kwan
authors.forename: R M
authors.initials: RM
authors.lastname: Wadsworth
authors.forename: K A
authors.initials: KA
authors.lastname: Kane
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D015232:Dinoprostone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D012701:Serotonin / Q000097:blood; D012756:Sheep; D013928:Thromboxane A2 / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D012701:Serotonin; D013928:Thromboxane A2; D000241:Adenosine; D015232:Dinoprostone; D000109:Acetylcholine; D009638:Norepinephrine