Administration of the Rho-kinase inhibitor, fasudil, following nitroglycerin additionally dilates the site of coronary spasm in patients with vasospastic angina

Otsuka, Toshiaki; Ibuki, Chikao; Suzuki, Takeshi; Ishii, Kensuke; Yoshida, Hiroshi; Kodani, Eitaro; Kusama, Yoshiki; Atarashi, Hirotsugu; Kuroda, Hiroshi; Takano, Teruo; Mizuno, Kyoichi

doi:10.1097/mca.0b013e3282f3420c

Cited by 36 publications

(18 citation statements)

References 29 publications

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“…These data suggest that, in normal mouse aorta, acetylcholine-induced NO-mediated responses are not sex dependent. Similar to previous studies (6,34), responses to acetylcholine and nitroprusside were enhanced in arteries from nondiabetic males following inhibition of rho kinase. The effect of inhibitors of rho kinase on responses of aorta from males was absent when NO synthase was inhibited or when responses to NO-mediated vasodilators were reduced, as in diabetes.…”

Section: Discussionsupporting

confidence: 86%

Sex-dependent differences in Rho activation contribute to contractile dysfunction in type 2 diabetic mice

Nuno

Harrod

Lamping

2009

American Journal of Physiology-Heart and Circulatory Physiology

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The objective of this study was to determine if mechanisms involved in vascular dysfunction in type 2 diabetes differ with sex. Vascular reactivity, expression, and activation of rhoA and rho kinase were measured in aorta from male and female nondiabetic C57BLKS/J and diabetic BKS.Cg-m(+/+) Lepr(db)/J (db/db) mice, a model of type 2 diabetes. Relaxation to acetylcholine and nitroprusside was similar in aorta from nondiabetic male and female mice. Relaxation to acetylcholine was reduced approximately 50% in both male and female diabetic mice. Although inhibition of rho kinase with H-1152 increased relaxation to acetylcholine and nitroprusside in nondiabetic males, it had no effect on the response in either nondiabetic or diabetic females or diabetic males. Contraction to serotonin was increased similarly in male and female diabetic mice compared with nondiabetic mice and was reduced following inhibition of rho kinase with either fasudil or H-1152. Activation of rhoA and its downstream effector, rho kinase, was greater in aorta from diabetic males compared with nondiabetic males. In contrast, there were no differences in vascular activation of rhoA or rho kinase in diabetic females. The increased activity of rhoA and rho kinase in diabetic mice was not due to a change in protein expression of rhoA or rho kinase (ROCK1 and ROCK2) in vessels from either males or females. Although contractile dysfunction in vessels occurs in both male and female diabetic mice, the dysfunction in diabetic males is dependent upon activation of rhoA and rho kinase. Alternative mechanisms affecting rho kinase activation may be involved in females.

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Section: Discussionsupporting

confidence: 86%

Sex-dependent differences in Rho activation contribute to contractile dysfunction in type 2 diabetic mice

Nuno

Harrod

Lamping

2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…Some studies show these cases: a swine case that intracoronary ''Fasudil'' 100 lg/kg inhibited vasospasm [8,14], a human case where systematic administration of fasudil is effective for vasospasm [15], and a human case in which a slow (more than 5 min) administration of intracoronary ''Fasudil'' treated vasospasm [14,16]. However, there has been no report that bolus administration of intracoronary ''Fasudil'' was effective for vasospasm.…”

Section: Discussionmentioning

confidence: 95%

The impact of Rho-kinase inhibitor, “Fasudil”, intracoronary bolus administration to improve refractory coronary vasospasm

Komiyama

Tejima

Tanabe

et al. 2011

Cardiovasc Interv and Ther

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A 57 year-old man presenting with acute inferior myocardial infarction underwent percutaneous coronary intervention. Following the placement of TAXUS Liberte 2.5 × 24 mm (Boston Sientific, USA), for 99% stenosis with delay, severe vasospasm occurred at distal portion of the stent. However, persistent vasospasm was observed despite ISDN (isosorbide dinitrate), nitroprusside, and nicorandil, were used to control the repetitive vasospasm during the course of 90 min. Then the decision was made to use intra-coronary bolus of Rho-kinase inhibitor, fasudil 100 μg/kg. Then the vasospasm resolved and no recurrence was observed during the procedure and hospital stay for 25 days. We experienced a valuable case, whose repetitive vasospasm was resolved with intracoronary administration of Rho kinase inhibitor.

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“…Fasudil further dilated the site of ACh-induced coronary vasospasm in patients with vasospastic angina already treated with NTG [ 83 ] and prevented the occurrence of myocardial ischemia in patients with microvascular angina [ 82 ]. Moreover, in patients with effort angina, intracoronary administration of fasudil significantly increased oxygen saturation in the coronary sinus vein and ameliorated pacing-induced myocardial ischemia, including symptoms, ischemic ST-segment depression and lactate production [ 12 ].…”

Section: Fasudil a Rho-kinase Inhibitormentioning

confidence: 94%

New Antianginal Drugs Still Not Available for Clinical Use

Tamargo

Delpón

2015

Pharmacological Treatment of Chronic Stable Angina Pectoris

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Administration of the Rho-kinase inhibitor, fasudil, following nitroglycerin additionally dilates the site of coronary spasm in patients with vasospastic angina

Abstract: Fasudil further dilated the site of coronary spasm, which had already been treated with NTG in patients with vasospastic angina. These findings support and extend the previous results that showed the feasibility of employing fasudil as a novel therapeutic approach for coronary spasm.

Cited by 36 publications

References 29 publications

Sex-dependent differences in Rho activation contribute to contractile dysfunction in type 2 diabetic mice

Sex-dependent differences in Rho activation contribute to contractile dysfunction in type 2 diabetic mice

The impact of Rho-kinase inhibitor, “Fasudil”, intracoronary bolus administration to improve refractory coronary vasospasm

New Antianginal Drugs Still Not Available for Clinical Use

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