Activation of Rho-kinase in the brainstem enhances sympathetic drive in mice with heart failure

Koji Ito, Yoshikuni Kimura, Yoshitaka Hirooka, Yoji Sagara, Kenji Sunagawa

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Rho-kinase is involved in the pathogenesis of hypertension and left ventricular remodelling after myocardial infarction (MI). In an earlier study, we had demonstrated that Rho-kinase in the brainstem contributes to hypertensive mechanisms via the sympathetic nervous system; however, it is not known whether Rho-kinase in the brainstem also contributes to sympathetic nerve activation after MI. Male Institute of Cancer Research mice (8-10 weeks old) were used for the study. Two days before coronary artery occlusion (MI group), the left ventricular function was estimated by echocardiography. Following this, Y-27632 (0.5 mM, 0.25 μL/h), a specific Rho-kinase inhibitor, or a vehicle was intracisternally infused in the mice using an osmotic mini-pump. Nine days after coronary artery occlusion, we evaluated the 24-hour urinary norepinephrine excretion (U-NE) as a marker of sympathetic nerve activity. Ten days after coronary artery occlusion, we measured organ weight and evaluated Rho-kinase activity in the brainstem by measuring the amount of phosphorylated ezrin/radixin/moesin proteins, one of the substrates of Rho-kinase. The control group underwent a sham operation. Rho-kinase activity, U-NE, and lungs and liver weight were significantly greater in the MI group compared with the control group. Left ventricular size increased and percent fractional shortening decreased in the MI group compared with the control group. Y-27632 significantly decreased Rho-kinase activity and attenuated the increase in U-NE after MI. These results demonstrate that Rho-kinase is activated in the brainstem after MI and that the activation of this pathway is involved in the resulting enhanced sympathetic drive.

Original languageEnglish
Pages (from-to)77-81
Number of pages5
JournalAutonomic Neuroscience: Basic and Clinical
Volume142
Issue number1-2
DOIs
Publication statusPublished - Nov 3 2008

All Science Journal Classification (ASJC) codes

  • Endocrine and Autonomic Systems
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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