Effects of hydroxyfasudil administered to the nucleus tractus solitarii on blood pressure and heart rate in spontaneously hypertensive rats

Koji Ito, Yoshitaka Hirooka, Yoshikuni Kimura, Hiroaki Shimokawa, Akira Takeshita

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Abstract

Previously, we reported that the inhibition of Rho-kinase by a microinjection of Y-27632 or the transfection of dominant-negative Rho-kinase into cells of the nucleus tractus solitani (NTS) reduces blood pressure, heart rate, and sympathetic nerve activity. In the present study, we examined the effects of another Rho-kinase inhibitor, hydroxyfasudil, on blood pressure and heart rate in anesthetized rats. The results were compared between normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The microinjection of hydroxyfasudil was performed unilaterally or bilaterally into the NTS of WKY rats and SHR. A unilateral microinjection of hydroxyfasudil elicited depressor and bradycardic responses in SHR but not in WKY rats. A bilateral microinjection of hydroxyfasudil elicited depressor and bradycardic responses in both SHR and WKY rats. However, the magnitude of the decrease in these variables was greater in SHR than in WKY rats. The expression levels of RhoA in the membrane fraction and phosphorylated ERM family (ezrin, radixin, and moesin) in the NTS were greater in SHR than in WKY rats. These results suggest that the microinjection of hydroxyfasudil into the NTS causes cardiovascular responses similar to those caused by Y-27632 and that these responses are probably mediated by the inhibition of Rho-kinase.

Original languageEnglish
Pages (from-to)269-277
Number of pages9
JournalClinical and Experimental Hypertension
Volume27
Issue number2-3
DOIs
Publication statusPublished - Feb 1 2005

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Solitary Nucleus
Inbred WKY Rats
Inbred SHR Rats
Microinjections
rho-Associated Kinases
Heart Rate
Blood Pressure
Cell Nucleus
Transfection
hydroxyfasudil
Membranes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology

Cite this

Effects of hydroxyfasudil administered to the nucleus tractus solitarii on blood pressure and heart rate in spontaneously hypertensive rats. / Ito, Koji; Hirooka, Yoshitaka; Kimura, Yoshikuni; Shimokawa, Hiroaki; Takeshita, Akira.

In: Clinical and Experimental Hypertension, Vol. 27, No. 2-3, 01.02.2005, p. 269-277.

Research output: Contribution to journalArticle

Ito, Koji ; Hirooka, Yoshitaka ; Kimura, Yoshikuni ; Shimokawa, Hiroaki ; Takeshita, Akira. / Effects of hydroxyfasudil administered to the nucleus tractus solitarii on blood pressure and heart rate in spontaneously hypertensive rats. In: Clinical and Experimental Hypertension. 2005 ; Vol. 27, No. 2-3. pp. 269-277.
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