Chronic fluvastatin treatment alters vascular contraction by inhibiting the Rho/Rho-kinase pathway.
1. In the present study, we investigated the effects of chronic treatment of stroke-prone spontaneously hypertensive rats (SHRSP) with the statin fluvastatin on vascular Rho/Rho-kinase pathway mediated contraction, which has been shown to be upregulated in hypertension. 2. Contribution of the Rho/Rho-kinase pathway to noradrenaline-induced contraction of arteries from SHRSP was assessed by the inhibitory effect of Y-27632, a Rho/Rho-kinase inhibitor. Stroke-prone spontaneously hypertensive rats were treated with fluvastatin (10 mg/kg per day) for 1 month. 3. Treatment with fluvastatin tended to attenuate the contraction to noradrenaline and significantly decreased the Y-27632-sensitive component of the contraction in controls compared with fluvastatin-treated rats. 4. RhoA, as assessed by western blotting, was also reduced by fluvastatin treatment. 5. These findings suggest that chronic treatment with fluvastatin reduces the contractile response associated with Rho/Rho-kinase in arteries of hypertensive rats.
Kansui
Yasuo
Y
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Fujii
Koji
K
Goto
Kenichi
K
Oniki
Hideyuki
H
Iida
Mitsuo
M
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000577:Amides; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014662:Vasoconstrictor Agents; C108830:Y 27632; D000077340:Fluvastatin; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D009638:Norepinephrine