An analysis of the nitrate‐like and K channel opening actions of KRN2391 in canine coronary arterial smooth muscle

Okada, Yuji; Yanagisawa, Teruyuki; Taira, Norio

doi:10.1111/j.1476-5381.1991.tb12514.x

Cited by 34 publications

(20 citation statements)

References 33 publications

(39 reference statements)

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“…However, cromakalim produced insufficient relaxation even at a concentration showing maximum effect. The present results with KRN2391, nicorandil and cromakalim are in good agree ment with the previous results using the same preparation (5,17,21). This insufficient relaxation by cromakalim seemed to be based on the finding that the relaxant effect of a K-channel opener in vascular smooth muscle contract ed by KCl depends on the concentration of KCl (21).…”

Section: Discussionsupporting

confidence: 81%

“…In isolated canine small coronary artery, KRN2391-induced relaxation was antagonized by either methylene blue or glibenclamide. Furthermore, Okada et al (5) reported in detail that KRN2391 possessed a dual mechanism of action by examining its effects on both intracellular calcium concentration and force in canine small coronary artery. These findings in isolated small coronary artery are different from the present results which were obtained in isolated canine large coronary artery.…”

Section: Discussionmentioning

confidence: 99%

“…The vasodilating mechanism of KRN2391 is thought to be based on its dual mechanism of action as a nitrate and a K-channel opener because KRN2391-induced relaxation was inhibited by K channel blockers and an inhibitor of soluble guanylate cyclase in isolated rat (3) and rabbit (4) aorta and isolated canine small coronary artery (5). Nicorandil is also report ed to possess such a dual mechanism of action (6).…”

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confidence: 99%

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Mechanism of Action of KRN2391 in Canine Coronary Vascular Bed

Fukata

Kaneta

Okada

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-The present studies were performed to clarify the mechanism of action of KRN2391 in various sizes of canine coronary artery. We used the responses of isolated large and small coronary arteries and the changes in coronary blood flow (CBF) as indicators reflecting the responses of conductive arteries and resistive arterioles, respectively. In isolated small coronary artery, the effect of KRN2391 (10-8-10-5 M) was antagonized by either methylene blue or glibenclamide. In isolated large coronary artery, the vasorelaxant effect of KRN2391 (10-'-10-'M) and nicorandil (10-'-10-4 M) were antagonized by methylene blue (10-'M) but not by glibenclamide (10-'M). The relaxant effect of cromakalim was an tagonized by glibenclamide but not by methylene blue in isolated large coronary artery. Intracoronary arterial injection of KRN2391, nicorandil or cromakalim produced an increase in CBF dose-dependently. Glibenclamide (5 mg/kg, i.v.) attenuated the increase in CBF caused by KRN2391, nicorandil and cromakalim. ED20, the dose that produced an increase in CBF by 20 ml/min, increased about 5-fold for KRN2391 and nicorandil and about 12-fold for cromakalim after administration of glibenclamide. These results suggest that the mechanism of action of KRN2391 and nicorandil depends on the segment of coro nary arteries; i.e., they show a nitrate action alone in large coronary artery, and a K-channel opening action in addition to a nitrate action as the size of the coronary artery decreases.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Mechanism of Action of KRN2391 in Canine Coronary Vascular Bed

Fukata

Kaneta

Okada

et al. 1993

Japanese Journal of Pharmacology

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“…KRN2391 and nicorandil act as a nitrate alone in canine large coronary artery because KRN2391 and nicorandil-induced relaxations were in hibited by methylene blue but not by glibenclamide in iso lated canine large coronary artery (7,12). Both K channel opening and nitrate-like actions can be demonstrated in canine small coronary artery (15). In contrast, KRN2391 and nicorandil act predominantly as a K channel opener in resistive coronary arterioles because the increase in coronary blood flow induced by KRN2391 and nicorandil was inhibited by pretreatment with glibenclamide in anesthetized dog (14,21).…”

Section: Discussionmentioning

confidence: 94%

“…In coronary arteries, it has been demonstrated that the behaviors of KRN2391 and nicorandil depend on the segment of coro nary artery; i.e., they act as a nitrate in large coronary ar tery (7,12) and as a K channel opener in resistive coro nary arterioles (13,14). Both K channel opening and ni trate-like actions can be demonstrated in canine small coro nary artery (15). However, the mechanisms of action of KRN2391 and nicorandil in mesenteric artery remain unclear despite showing relatively potent effects on mesen teric blood flow and coronary blood flow.…”

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confidence: 99%