Rho-kinase inhibitor improves increased vascular resistance and impaired vasodilation of the forearm in patients with heart failure

Takuya Kishi, Yoshitaka Hirooka, Akihiro Masumoto, Koji Ito, Yoshikuni Kimura, Kosuke Inokuchi, Tatsuya Tagawa, Hiroaki Shimokawa, Akira Takeshita, Kenji Sunagawa

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Background-Rho-kinase is suggested to have an important role in enhanced vasoconstriction in animal models of heart failure (HF). Patients with HF are characterized by increased vasoconstriction and reduced vasodilator responses to reactive hyperemia and exercise. The aim of the present study was to examine whether Rho-kinase is involved in the peripheral circulation abnormalities of HF in humans with the Rho-kinase inhibitor fasudil. Methods and Results-Studies were performed in patients with HF (HF group, n = 26) and an age-matched control group (n = 26). Forearm blood flow was measured with a strain-gauge plethysmograph during intra-arterial infusion of graded doses of fasudil or sodium nitroprusside. Resting forearm vascular resistance (FVR) was significantly higher in the HF group than in the control group. The increase in forearm blood flow evoked by fasudil was significantly greater in the HF group than in the control group. The increased FVR was decreased by fasudil in the HF group toward the level of the control group. By contrast, FVR evoked by sodium nitroprusside was comparable between the 2 groups. Fasudil significantly augmented the impaired ischemie vasodilation during reactive hyperemia after arterial occlusion of the forearm in the HF group but not in the control group. Fasudil did not augment the increased FVR evoked by phenylephrine in the control group significantly. Conclusions-These results indicate that Rho-kinase is involved in increased FVR and impaired vasodilation of the forearm in patients with HF.

Original languageEnglish
Pages (from-to)2741-2747
Number of pages7
JournalCirculation
Volume111
Issue number21
DOIs
Publication statusPublished - May 31 2005

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rho-Associated Kinases
Forearm
Vasodilation
Vascular Resistance
Heart Failure
Control Groups
Hyperemia
Nitroprusside
Vasoconstriction
Intra Arterial Infusions
Phenylephrine
Vasodilator Agents
fasudil
Research Design
Animal Models
Exercise

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Rho-kinase inhibitor improves increased vascular resistance and impaired vasodilation of the forearm in patients with heart failure. / Kishi, Takuya; Hirooka, Yoshitaka; Masumoto, Akihiro; Ito, Koji; Kimura, Yoshikuni; Inokuchi, Kosuke; Tagawa, Tatsuya; Shimokawa, Hiroaki; Takeshita, Akira; Sunagawa, Kenji.

In: Circulation, Vol. 111, No. 21, 31.05.2005, p. 2741-2747.

Research output: Contribution to journalArticle

Kishi, T, Hirooka, Y, Masumoto, A, Ito, K, Kimura, Y, Inokuchi, K, Tagawa, T, Shimokawa, H, Takeshita, A & Sunagawa, K 2005, 'Rho-kinase inhibitor improves increased vascular resistance and impaired vasodilation of the forearm in patients with heart failure', Circulation, vol. 111, no. 21, pp. 2741-2747. https://doi.org/10.1161/CIRCULATIONAHA.104.510248
Kishi, Takuya ; Hirooka, Yoshitaka ; Masumoto, Akihiro ; Ito, Koji ; Kimura, Yoshikuni ; Inokuchi, Kosuke ; Tagawa, Tatsuya ; Shimokawa, Hiroaki ; Takeshita, Akira ; Sunagawa, Kenji. / Rho-kinase inhibitor improves increased vascular resistance and impaired vasodilation of the forearm in patients with heart failure. In: Circulation. 2005 ; Vol. 111, No. 21. pp. 2741-2747.
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AU - Hirooka, Yoshitaka

AU - Masumoto, Akihiro

AU - Ito, Koji

AU - Kimura, Yoshikuni

AU - Inokuchi, Kosuke

AU - Tagawa, Tatsuya

AU - Shimokawa, Hiroaki

AU - Takeshita, Akira

AU - Sunagawa, Kenji

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N2 - Background-Rho-kinase is suggested to have an important role in enhanced vasoconstriction in animal models of heart failure (HF). Patients with HF are characterized by increased vasoconstriction and reduced vasodilator responses to reactive hyperemia and exercise. The aim of the present study was to examine whether Rho-kinase is involved in the peripheral circulation abnormalities of HF in humans with the Rho-kinase inhibitor fasudil. Methods and Results-Studies were performed in patients with HF (HF group, n = 26) and an age-matched control group (n = 26). Forearm blood flow was measured with a strain-gauge plethysmograph during intra-arterial infusion of graded doses of fasudil or sodium nitroprusside. Resting forearm vascular resistance (FVR) was significantly higher in the HF group than in the control group. The increase in forearm blood flow evoked by fasudil was significantly greater in the HF group than in the control group. The increased FVR was decreased by fasudil in the HF group toward the level of the control group. By contrast, FVR evoked by sodium nitroprusside was comparable between the 2 groups. Fasudil significantly augmented the impaired ischemie vasodilation during reactive hyperemia after arterial occlusion of the forearm in the HF group but not in the control group. Fasudil did not augment the increased FVR evoked by phenylephrine in the control group significantly. Conclusions-These results indicate that Rho-kinase is involved in increased FVR and impaired vasodilation of the forearm in patients with HF.

AB - Background-Rho-kinase is suggested to have an important role in enhanced vasoconstriction in animal models of heart failure (HF). Patients with HF are characterized by increased vasoconstriction and reduced vasodilator responses to reactive hyperemia and exercise. The aim of the present study was to examine whether Rho-kinase is involved in the peripheral circulation abnormalities of HF in humans with the Rho-kinase inhibitor fasudil. Methods and Results-Studies were performed in patients with HF (HF group, n = 26) and an age-matched control group (n = 26). Forearm blood flow was measured with a strain-gauge plethysmograph during intra-arterial infusion of graded doses of fasudil or sodium nitroprusside. Resting forearm vascular resistance (FVR) was significantly higher in the HF group than in the control group. The increase in forearm blood flow evoked by fasudil was significantly greater in the HF group than in the control group. The increased FVR was decreased by fasudil in the HF group toward the level of the control group. By contrast, FVR evoked by sodium nitroprusside was comparable between the 2 groups. Fasudil significantly augmented the impaired ischemie vasodilation during reactive hyperemia after arterial occlusion of the forearm in the HF group but not in the control group. Fasudil did not augment the increased FVR evoked by phenylephrine in the control group significantly. Conclusions-These results indicate that Rho-kinase is involved in increased FVR and impaired vasodilation of the forearm in patients with HF.

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