Inhibition of Rho-kinase in the brainstem augments baroreflex control of heart rate in rats

Koji Ito, Yoshitaka Hirooka, Yoji Sagara, Yoshikuni Kimura, Kozo Kaibuchi, Hiroaki Shimokawa, Akira Takeshita, Kenji Sunagawa

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The Rho/Rho-kinase pathway in the nucleus tractus solitarii (NTS) of the brain stem contributes to blood pressure regulation. Activation of this pathway might be involved in the central nervous system mechanisms of hypertension. The aim of the present study was to determine whether baroreflex control of heart rate is altered by inhibition of Rho-kinase in the NTS. Adenovirus vectors encoding dominant-negative Rho-kinase or β-galactosidase were transfected into the nucleus tractus solitarii of Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Baroreflex control of heart rate was examined by changing arterial pressure with an intravenous infusion of phenylephrine or sodium nitroprusside. The maximum gain of baroreflex control of heart rate was attenuated in SHR compared with WKY before the gene transfer. Transfection of adenovirus vectors encoding dominant-negative Rho-kinase significantly augmented the maximum gain in both WKY and SHR. The extent of this augmentation, however, was greater in SHR than in WKY. After treatment with metoprolol, the maximum gain was significantly decreased in rats transfected with adenovirus vectors encoding dominant-negative Rho-kinase, but not in nontransfected rats. In contrast, after treatment with atropine, the maximum gain was greater in rats transfected with adenovirus vectors encoding dominant-negative Rho-kinase compared with nontransfected rats, although it was decreased in both groups. These results suggest that inhibition of Rho-kinase in the NTS augments baroreflex control of heart rate, in both WKY and SHR, probably because of a cardiac sympathoinhibitory effect.

Original languageEnglish
Pages (from-to)478-483
Number of pages6
JournalHypertension
Volume44
Issue number4
DOIs
Publication statusPublished - Oct 1 2004

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rho-Associated Kinases
Baroreflex
Brain Stem
Inbred WKY Rats
Heart Rate
Inbred SHR Rats
Solitary Nucleus
Adenoviridae
Galactosidases
Metoprolol
Nitroprusside
Phenylephrine
Atropine
Intravenous Infusions
Transfection
Arterial Pressure
Central Nervous System
Blood Pressure
Hypertension
Therapeutics

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Ito, K., Hirooka, Y., Sagara, Y., Kimura, Y., Kaibuchi, K., Shimokawa, H., ... Sunagawa, K. (2004). Inhibition of Rho-kinase in the brainstem augments baroreflex control of heart rate in rats. Hypertension, 44(4), 478-483. https://doi.org/10.1161/01.HYP.0000143120.24612.68

Inhibition of Rho-kinase in the brainstem augments baroreflex control of heart rate in rats. / Ito, Koji; Hirooka, Yoshitaka; Sagara, Yoji; Kimura, Yoshikuni; Kaibuchi, Kozo; Shimokawa, Hiroaki; Takeshita, Akira; Sunagawa, Kenji.

In: Hypertension, Vol. 44, No. 4, 01.10.2004, p. 478-483.

Research output: Contribution to journalArticle

Ito, K, Hirooka, Y, Sagara, Y, Kimura, Y, Kaibuchi, K, Shimokawa, H, Takeshita, A & Sunagawa, K 2004, 'Inhibition of Rho-kinase in the brainstem augments baroreflex control of heart rate in rats', Hypertension, vol. 44, no. 4, pp. 478-483. https://doi.org/10.1161/01.HYP.0000143120.24612.68
Ito, Koji ; Hirooka, Yoshitaka ; Sagara, Yoji ; Kimura, Yoshikuni ; Kaibuchi, Kozo ; Shimokawa, Hiroaki ; Takeshita, Akira ; Sunagawa, Kenji. / Inhibition of Rho-kinase in the brainstem augments baroreflex control of heart rate in rats. In: Hypertension. 2004 ; Vol. 44, No. 4. pp. 478-483.
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