Effects of hydroxyfasudil administered to the nucleus tractus solitarii on blood pressure and heart rate in spontaneously hypertensive rats.
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 solitarii (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.
Ito
Koji
K
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Hirooka
Yoshitaka
Y
Kimura
Yoshikuni
Y
Shimokawa
Hiroaki
H
Takeshita
Akira
A
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008845:Microinjections; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017552:Solitary Nucleus / Q000187:drug effects* / Q000201:enzymology; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; C431085:hydroxyfasudil; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein