Effect of K+ channel-modulating drugs on the vasoconstrictor responses of leukotrienes C4, D4 and angiotensin II in the guinea-pig isolated perfused heart.

1. The vascular actions of leukotrienes C4 (LTC4) and LTD4 in the guinea-pig isolated perfused heart were studied in the presence of potassium (K+) channel modulatory compounds. 2. Cromakalim (0.35-10 microM), a K+ channel activator, inhibited the vasoconstrictor responses of LTC4 (30 pmol), LTD4 (30 pmol) and angiotensin II (AII) (100 pmol) in a concentration-dependent manner. 3. Glyceryl trinitrate (10 mgl-1) and vasoactive intestinal peptide (10 nM) induced a similar vasodilator action to cromakalim in the isolated heart but had no effect on responses to LTC4 and LTD4. 4. The inhibitory action by cromakalim (10 microM) on the LTC4 (30 pmol) response could be reversed in the presence of an equimolar concentration of glibenclamide. However, glibenclamide (10 microM) only partially restored the LTD4 (30 pmol) actions. 5. Galanin (10 nM) and charybdotoxin (60 nM) had no effect on the vascular responses to LTC4 and LTD4 (30 pmol). 6. Inhibition by cromakalim of coronary vasospasm induced by vascular LTC4, LTD4 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 LTC4, LTD4 and AII.