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

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 pinacidil was more potent than levcromakalim and aprikalim against the contractions induced by carbachol (0.001-10 muM) or K+ (5-50 mM). Whereas levcromakalim and aprikalim acted only at low concentrations of K+, the rightward shift of the K+ concentration-effect curve produced by pinacidil was observed at all K+ concentrations (5-50 mM), suggesting that a mechanism of action other than K+ channel opening is involved in the effects of pinacidil. Pinacidil (0.3-100 muM) had the greatest spasmolytic effect in airways precontracted by carbachol (0.3 muM). The three K+ channel openers were equipotent against the sustained contractions of airways induced by 25 or 30 mM K+ and their spasmolytic activity was more marked against contractions induced by low rather low than high K+ concentrations. Levcromakalim and aprikalim were more effective as relaxant than as antispasmodic drugs. In K+-precontracted pulmonary vessels, the relaxant activity of pinacidil and levcromakalim was more pronounced than that observed in airways, suggesting a vascular selectivity of these drugs.