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Abstract

Effect of accumulation of NKY-722, a water-soluble vasoselective Ca++ antagonist, on KCl-induced contraction in isolated canine mesenteric arteries.

H Shimaji, H Shirahase, M Kanda, S Osumi and K Kurahashi
Journal of Pharmacology and Experimental Therapeutics August 1991, 258 (2) 676-680;
H Shimaji
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H Shirahase
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M Kanda
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S Osumi
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K Kurahashi
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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.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 258, Issue 2
1 Aug 1991
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Abstract

Effect of accumulation of NKY-722, a water-soluble vasoselective Ca++ antagonist, on KCl-induced contraction in isolated canine mesenteric arteries.

H Shimaji, H Shirahase, M Kanda, S Osumi and K Kurahashi
Journal of Pharmacology and Experimental Therapeutics August 1, 1991, 258 (2) 676-680;

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Abstract

Effect of accumulation of NKY-722, a water-soluble vasoselective Ca++ antagonist, on KCl-induced contraction in isolated canine mesenteric arteries.

H Shimaji, H Shirahase, M Kanda, S Osumi and K Kurahashi
Journal of Pharmacology and Experimental Therapeutics August 1, 1991, 258 (2) 676-680;
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