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

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 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.

• Authors: Takuya Kishi, Yoshitaka Hirooka, Akihiro Masumoto, Koji Ito, Yoshikuni Kimura, Kosuke Inokuchi, Tatsuya Tagawa, Hiroaki Shimokawa, Akira Takeshita, Kenji Sunagawa
• Journal: Circulation (Circulation) Vol. 111 Issue 21 Pg. 2741-7 (May 31 2005) ISSN: 1524-4539 [Electronic] United States
• PMID: 15927989 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intracellular Signaling Peptides and Proteins
• Protein Kinase Inhibitors
• Nitroprusside
• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• Protein Serine-Threonine Kinases
• rho-Associated Kinases
• fasudil

Topics

• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (administration & dosage, analogs & derivatives, pharmacology)
• Aged
• Case-Control Studies
• Dose-Response Relationship, Drug
• Female
• Forearm (blood supply)
• Heart Failure (drug therapy, physiopathology)
• Humans
• Intracellular Signaling Peptides and Proteins
• Male
• Middle Aged
• Nitroprusside (administration & dosage, pharmacology)
• Protein Kinase Inhibitors (administration & dosage, pharmacology)
• Protein Serine-Threonine Kinases (antagonists & inhibitors)
• Regional Blood Flow (drug effects)
• Vascular Resistance (drug effects)
• Vasodilation (drug effects)
• rho-Associated Kinases