EFFECTS OF 3 K-PIG LUNG( CHANNEL OPENERS ON AIRWAYS AND PULMONARY CIRCULATION IN THE ISOLATED GUINEA)

The antispasmodic and spasmolytic effects of levcromakalim (BRL 38227) , aprikalim (RP 52891) and pinacidil were investigated in airways and pulmonary vessels of the isolated guinea-pig perfused lung. In airways , the three drugs exhibited modest antispasmodic properties, and pinac idil was more potent than levcromakalim and aprikalim against the cont ractions induced by carbachol (0.001-10 muM) or K+ (5-50 mM). Whereas levcromakalim and aprikalim acted only at low concentrations of K+, th e rightward shift of the K+ concentration-effect curve produced by pin acidil was observed at all K+ concentrations (5-50 mM), suggesting tha t a mechanism of action other than K+ channel opening is involved in t he effects of pinacidil. Pinacidil (0.3-100 muM) had the greatest spas molytic effect in airways precontracted by carbachol (0.3 muM). The th ree K+ channel openers were equipotent against the sustained contracti ons of airways induced by 25 or 30 mM K+ and their spasmolytic activit y was more marked against contractions induced by low rather low than high K+ concentrations. Levcromakalim and aprikalim were more effectiv e as relaxant than as antispasmodic drugs. In K+-precontracted pulmona ry vessels, the relaxant activity of pinacidil and levcromakalim was m ore pronounced than that observed in airways, suggesting a vascular se lectivity of these drugs.