Effect of accumulation of NKY-722, a water-soluble vasoselective Ca++ antagonist, on KCl-induced contraction in isolated canine mesenteric arteries.
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.
Shimaji
H
H
Department of Pharmacology, Kyoto University, Japan.
Shirahase
H
H
Kanda
M
M
Osumi
S
S
Kurahashi
K
K
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*
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C058351:NKY 722; D011189:Potassium Chloride