Fasudil attenuates sympathetic nervous activity in the adrenal medulla of spontaneously hypertensive rats.
We investigated the effects of fasudil, a Rho kinase inhibitor, on hypertension in spontaneously hypertensive rats and on the catecholamine synthetic pathway. Ten-week-old male SHR and Wistar-Kyoto rats were administered fasudil (10 mg/kg/day s.c.) for 4 days. Systolic blood pressure was measured using the tail-cuff method. Catecholamine levels were measured with high-performance liquid chromatography-ECD methods. Tyrosine hydroxylase protein levels were measured in Western blot analysis. The tyrosine hydroxylase mRNA level was measured using real-time PCR methods. Fasudil significantly decreased systolic blood pressure in spontaneously hypertensive rats, but not in Wistar-Kyoto rats. Fasudil also significantly decreased catecholamine, tyrosine hydroxylase protein, and tyrosine hydroxylase mRNA levels in the adrenal medulla of spontaneously hypertensive rats. These results suggest that the depressor effects of fasudil on hypertension in spontaneously hypertensive rats may be related to inhibition of the catecholamine synthetic pathway.
Kumai
Toshio
T
Department of Pharmacology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 2168511, Japan. yakuri@marianna-u.ac.jp
Takeba
Yuko
Y
Matsumoto
Naoki
N
Nakaya
Sachiko
S
Tsuzuki
Yoshimitsu
Y
Yanagida
Yohei
Y
Hayashi
Mikito
M
Kobayashi
Shinichi
S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000313:Adrenal Medulla / Q000187:drug effects* / Q000294:innervation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D002395:Catecholamines / Q000097:blood / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D014446:Tyrosine 3-Monooxygenase; C049347:fasudil; D009638:Norepinephrine; D004837:Epinephrine