Effects of three 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 microM) 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 microM) had the greatest spasmolytic effect in airways precontracted by carbachol (0.3 microM). 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.
Dumas
M
M
Laboratoire de Pharmacologie, Faculté de Médecine Paris-Ouest, France.
Dumas
J P
JP
Advenier
C
C
Giudicelli
J F
JF
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010847:Picolines / Q000494:pharmacology*; D020110:Pinacidil; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011652:Pulmonary Circulation / Q000187:drug effects; D011714:Pyrans / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*
D001578:Benzopyrans; D006146:Guanidines; D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; D011758:Pyrroles; D019806:Cromakalim; C061043:aprikalim; D020110:Pinacidil; D011188:Potassium