Effect of levcromakalim on hypoxia-, KCl- and prostaglandin F2 alpha-induced contractions in isolated rat pulmonary artery.
The effect of levcromakalim on vascular reactivity was examined in rat isolated pulmonary arterial (PA) rings. Vasoconstriction in response to KCl, prostaglandin F2 alpha (PGF2 alpha) and hypoxia and vasodilatation in response to levcromakalim were studied isometrically in a small-vessel myograph. Levcromakalim caused a dose-dependent inhibition of hypoxic pulmonary vasoconstriction (HPV) in pulmonary resistance vessels (PRV). At 10 microM, levcromakalim caused 58% inhibition in PRV compared with control. In contrast, HPV in large PAs was not significantly inhibited by levcromakalim. At a higher concentration, levcromakalim (100 microM) caused 88% inhibition in PRV and 80% inhibition in PA. The first phase of HPV is not endothelium-dependent, but second-phase contraction is partially endothelium dependent. Levcromakalim (1-10 microM) inhibited contractions induced by low KCl concentrations (10-30 mM) and had no effect on those elicited by 50 to 100 mM KCl in PRV. However, a higher concentration of levcromakalim (100 microM) significantly decreased KCl efficacy in PRV. In PA, all of the concentrations of levcromakalim (1-100 microM) significantly decreased KCl efficacy. The vasorelaxant effects of levcromakalim (1-100 microM) on PRV and PA rings contracted with a low KCl concentration (30 mM) were prevented by tetrabutylammonium (10 microns). PGF2 alpha (1-100 microM)-induced contractions were diminished in both vessel types by levcromakalim (0.1-10 microM). The maximal response to PGF2 alpha was decreased by 77.72% in PRV and 68.50% in PA, respectively, in the presence of 10 microM levcromakalim. Levcromakalim (1 microM) has no additional effect on the transient contraction induced by PGF2 alpha in Ca(++)-free solution in PRV and PA.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine and Pharmacology, Royal Hallamshire Hospital, University of Sheffield, UK.
F
F
Zhang
A H
AH
Morice
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D019806:Cromakalim; D015237:Dinoprost / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D011758:Pyrroles; D000644:Quaternary Ammonium Compounds; D014665:Vasodilator Agents; D019806:Cromakalim; D011189:Potassium Chloride; D015237:Dinoprost; C009405:tetrabutylammonium; D002118:Calcium