title: Effect of accumulation of NKY-722, a water-soluble vasoselective Ca++ antagonist, on KCl-induced contraction in isolated canine mesenteric arteries.
abstract: The relationship between the accumulation of NKY-722 and its vasoinhibitory effect on KCl-induced contraction was examined in canine mesenteric arteries. NKY-722 showed a high level of accumulation in canine mesenteric arteries and reached near maximal levels at 60 min. The tissue/medium ratio measured at 60 min was independent of the bath concentration of NKY-722 (10(-9), 10(-8) and 10(-7) M). NKY-722 (10(-9) and 10(-7) M) attenuated the KCl (30 mM)-induced contraction of canine mesenteric arteries, and this effect was dependent on the pretreatment time (5-60 min). The vasoinhibitory effect of NKY-722 (during incubation) on KCl-induced contraction correlated with its accumulation in the vascular preparations. Preparations were incubated with NKY-722 (5 x 10(-9) M) for 60 min and repetitively washed out, showing that the accumulation of NKY-722 decreased slowly over 300 min. When the preparations were incubated with NKY-722 (5 x 10(-9) M) for 60 min, the vasoinhibitory effect on KCl-induced contraction remained for over 300 min after repetitive washouts. The vasoinhibitory effect of NKY-722 (during washout) on KCl-induced contraction also correlated with its accumulation in the vascular preparations. The present experiments indicate that NKY-722 accumulates in canine mesenteric arteries at high levels and should be washed out slowly, and suggest that NKY-722 accumulation in vessel walls may contribute to the long duration of its antihypertensive effect.
authors.affiliation: Department of Pharmacology, Kyoto University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shimaji
authors.forename: H
authors.initials: H
authors.lastname: Shirahase
authors.forename: M
authors.initials: M
authors.lastname: Kanda
authors.forename: S
authors.initials: S
authors.lastname: Osumi
authors.forename: K
authors.initials: K
authors.lastname: Kurahashi
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D004095:Dihydropyridines / Q000378:metabolism* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C058351:NKY 722; D011189:Potassium Chloride