Effect of ICI 198,615, SK+F 104,353, MK-571 and CGP45715A on cysteinyl leukotriene-induced responses in guinea-pig heart.
Peptidoleukotrienes (LTs), LTC4 and LTD4, cause potent vasoconstriction and myocardial depression in a range of species including man. The recent availability of specific LTD4 antagonists has allowed the evaluation of LT involvement in disease states and the characterisation of LT receptors in the airways. We decided to study the actions of four LT antagonists; ICI 198,615, SK + F 104,353, MK-571 and CGP45715A on LTD4-, LTC4- and U46619-induced effects in the coronary vasculature and on cardiac contractility in the guinea-pig isolated heart. We found a difference in the actions of the antagonists in the GP heart compared with the lung. ICI 198,615 retained its selectivity towards LTD4 whereas SK + F 104,353 antagonised both LTD4 and LTC4. MK-571 and CGP45715A had a non specific action against the LTs. Our results also indicated a direct action of the LTs on cardiac contractility which was not associated with the constriction of the coronary vasculature. These studies indicate that if the leukotrienes are involved in cardiac disease antagonists specific for the peptidoleukotrienes may be of therapeutic benefit in many of the disease states of the heart.
McLeod
J D
JD
Pharmacology Department, Hunterian Institute, Royal College of Surgeons, London.
Piper
P J
PJ
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D003998:Dicarboxylic Acids / Q000494:pharmacology; D006168:Guinea Pigs; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011422:Propionates / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
D001578:Benzopyrans; D003998:Dicarboxylic Acids; D007191:Indazoles; D011422:Propionates; D011450:Prostaglandin Endoperoxides, Synthetic; D011804:Quinolines; D013189:SRS-A; D014662:Vasoconstrictor Agents; C054217:ICI 198615; C059141:verlukast; C067425:iralukast; C052393:pobilukast