Effect of K + channel‐modulating drugs on the vasoconstrictor responses of leukotrienes C 4 , D 4 and angiotensin II in the guinea‐pig isolated perfused heart

1 The vascular actions of leukotrienes C 4 (LTC 4 ) and LTD 4 in the guinea‐pig isolated perfused heart were studied in the presence of potassium (K + ) channel modulatory compounds. 2 Cromakalim (0.35–10 μ m ), a K + channel activator, inhibited the vasoconstrictor responses of LTC 4 (30 pmol), LTD 4 (30 pmol) and angiotensin II (AII) (100 pmol) in a concentration‐dependent manner. 3 Glyceryl trinitrate (10 mgl −1 ) and vasoactive intestinal peptide (10 n m ) induced a similar vasodilator action to cromakalim in the isolated heart but had no effect on responses to LTC 4 and LTD 4 . 4 The inhibitory action by cromakalim (10 μ m ) on the LTC 4 (30 pmol) response could be reversed in the presence of an equimolar concentration of glibenclamide. However, glibenclamide (10 μ m ) only partially restored the LTD 4 (30 pmol) actions. 5 Galanin (10 n m ) and charybdotoxin (60 n m ) had no effect on the vascular responses to LTC 4 and LTD 4 (30 pmol). 6 Inhibition by cromakalim of coronary vasospasm induced by vascular LTC 4 , LTD 4 and AII appears to be separate from its vasodilator action and it is postulated that a cromakalim‐sensitive mechanism in the coronary vasculature is important in the vasoconstrictor responses to LTC 4 , LTD 4 and AII.