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(Circulation. 2005;111:2741-2747.)
© 2005 American Heart Association, Inc.

Heart Failure

Rho-Kinase Inhibitor Improves Increased Vascular Resistance and Impaired Vasodilation of the Forearm in Patients With Heart Failure

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

From the Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

Correspondence to Yoshitaka Hirooka, MD, PhD, FAHA, Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail hyoshi{at}cardiol.med.kyushu-u.ac.jp

Received September 30, 2004; revision received January 20, 2005; accepted February 23, 2005.

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 ischemic 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.

Key Words: heart failure • blood flow • vasoconstriction • vasodilation

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