TY - JOUR
T1 - An analysis of the nitrate‐like and K channel opening actions of KRN2391 in canine coronary arterial smooth muscle
AU - Okada, Yuji
AU - Yanagisawa, Teruyuki
AU - Taira, Norio
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1991/12
Y1 - 1991/12
N2 - To clarify the mechanism of action of KRN2391, a new vasodilator containing a nitroxy group, its effects on intracellular Ca2+ concentration ([Ca2+]i) and force of contraction in canine coronary artery were compared with those of two derivatives lacking the nitro group. KRN2391, its hydroxy and acetoxy derivative (Compound 2 and Compound 3, respectively) partially reduced [Ca2+]i in 5 or 30 mm KCl physiological salt solution (PSS), effects which were antagonized by glibenclamide. No KRN2391‐induced change in [Ca2+]i was observed in 90 mm KCl‐PSS. The order of potency in reducing [Ca2+]i and inhibiting the contracture in 30 mm KCl‐PSS was: KRN2391 > Compound 3 > Compound 2. In 30 mm KCl‐PSS, KRN2391 shifted the [Ca2+]i‐force relationship so that a greater increase in [Ca2+]i was needed to produce force. Compounds 2 and 3 were ineffective. The [Ca2+]i‐force curve obtained in 90 mm KCl‐PSS was shifted to the right by KRN2391 (10−4 m). The ability of KRN2391 to reduce the force of contraction in both 30 mm and 90 mm KCl‐PSS was inhibited by 10−5 m methylene blue. KRN2391 inhibited U46619‐induced contractions; this effect was associated with a reduction of [Ca2+]i, which decreased below the basal level. Thus, KRN2391 is a potent vasodilator in canine coronary artery. It possesses nitrate‐like and potassium channel opening actions and can be designated as a nitrate‐potassium channel opener (N‐K) hybrid. The denitrate derivatives of KRN2391 are specific K channel openers. The nitroxy moiety in KRN2391 is important for not only its action as a nitrate but also its potency as a K channel opener. 1991 British Pharmacological Society
AB - To clarify the mechanism of action of KRN2391, a new vasodilator containing a nitroxy group, its effects on intracellular Ca2+ concentration ([Ca2+]i) and force of contraction in canine coronary artery were compared with those of two derivatives lacking the nitro group. KRN2391, its hydroxy and acetoxy derivative (Compound 2 and Compound 3, respectively) partially reduced [Ca2+]i in 5 or 30 mm KCl physiological salt solution (PSS), effects which were antagonized by glibenclamide. No KRN2391‐induced change in [Ca2+]i was observed in 90 mm KCl‐PSS. The order of potency in reducing [Ca2+]i and inhibiting the contracture in 30 mm KCl‐PSS was: KRN2391 > Compound 3 > Compound 2. In 30 mm KCl‐PSS, KRN2391 shifted the [Ca2+]i‐force relationship so that a greater increase in [Ca2+]i was needed to produce force. Compounds 2 and 3 were ineffective. The [Ca2+]i‐force curve obtained in 90 mm KCl‐PSS was shifted to the right by KRN2391 (10−4 m). The ability of KRN2391 to reduce the force of contraction in both 30 mm and 90 mm KCl‐PSS was inhibited by 10−5 m methylene blue. KRN2391 inhibited U46619‐induced contractions; this effect was associated with a reduction of [Ca2+]i, which decreased below the basal level. Thus, KRN2391 is a potent vasodilator in canine coronary artery. It possesses nitrate‐like and potassium channel opening actions and can be designated as a nitrate‐potassium channel opener (N‐K) hybrid. The denitrate derivatives of KRN2391 are specific K channel openers. The nitroxy moiety in KRN2391 is important for not only its action as a nitrate but also its potency as a K channel opener. 1991 British Pharmacological Society
KW - K channel opener
KW - KRN2391
KW - N‐K hybrid
KW - dog coronary artery
KW - fura‐2
KW - glibenclamide
KW - intracellular calcium concentration
KW - nitrate
KW - relaxation
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U2 - 10.1111/j.1476-5381.1991.tb12514.x
DO - 10.1111/j.1476-5381.1991.tb12514.x
M3 - Article
C2 - 1810597
AN - SCOPUS:0025840148
VL - 104
SP - 829
EP - 838
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 4
ER -