TY - JOUR
T1 - Effects of hydroxyfasudil administered to the nucleus tractus solitarii on blood pressure and heart rate in spontaneously hypertensive rats
AU - Ito, Koji
AU - Hirooka, Yoshitaka
AU - Kimura, Yoshikuni
AU - Shimokawa, Hiroaki
AU - Takeshita, Akira
N1 - Funding Information:
This work was supported by grant-in-aid for scientific research from the Ministry of Education, Science, Sports, and Culture (C13670721, C15590757) and by a grant for Research on Autonomic Nervous System and Hypertension from Kimura Memorial Heart Foundation/Pfizer Pharmaceuticals, Inc.
PY - 2005/2
Y1 - 2005/2
N2 - 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.
AB - 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.
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U2 - 10.1081/CEH-200048876
DO - 10.1081/CEH-200048876
M3 - Article
C2 - 15835390
AN - SCOPUS:16444365371
VL - 27
SP - 269
EP - 277
JO - Clinical and Experimental Hypertension
JF - Clinical and Experimental Hypertension
SN - 1064-1963
IS - 2-3
ER -