title: Vasodilating effects of tetrazepam in isolated vascular smooth muscles: comparison with cromakalim and diltiazem.
abstract: The vasodilating effects of tetrazepam (1,4-benzodiazepine derivative) were studied and compared with those of the K-channel activator, cromakalim and the Ca-channel blocker, diltiazem, in rat aorta smooth muscle and on the spontaneous contractile activity of the rat portal vein. In the aorta, tetrazepam (3 x 10(-7)-10(-4) M) and diltiazem (10(-8)-3 x 10(-6) M) concentration-dependently relaxed aortic rings contracted by 30 mM as well as 80 m KCl. Although cromakalim (10(-8)-3 x 10(-6) M) concentration-dependently relaxed aortic rings contracted by 30 mM KCl, it did not relax those contrated by 80 mm KCl. In the presence of the ATP-sensitive K-channel blocker, glibenclamide (10(-6) and 3 x 10(-6) M), 30 mM KCl concentration-response curves for the relaxant effect of tetrazepam and diltiazem were unaffected but cromakalim caused a progressive shift of these curves upwards. In the portal vein, tetrazepam inhibited spontaneous contractions, decreased amplitude and increased frequency. Similar behaviour was shown with diltiazem (10(-8)-10(-5) M) and in both cases, pre-treatment with glibenclamide (10(-6) M) was ineffective. Although cromakalim (10(-5)-10(-6) M) decreased both amplitude and frequency, this effect was blocked by glibenclamide. These results indicate that the vasodilator action of tetrazepam is not mediated to the opening of ATP-sensitive K-channels, unlike cromakalim. This may be mediated, like those of diltiazem, by the blockade of calcium movements across the cell membrane.
authors.affiliation: Laboratorio de Farmacología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, España.
authors.forename: C
authors.initials: C
authors.lastname: Pérez-Guerrero
authors.forename: J
authors.initials: J
authors.lastname: Suárez
authors.forename: M D
authors.initials: MD
authors.lastname: Herrera
authors.forename: E
authors.initials: E
authors.lastname: Marhuenda
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D019806:Cromakalim / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000819:agonists*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D002121:Calcium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D001569:Benzodiazepines; D004110:Diltiazem; C005245:tetrazepam