Regulation of vascular tone from spontaneously hypertensive rats by the HMG-CoA reductase inhibitor, simvastatin.
The acute effect of simvastatin on aortic rings from spontaneously hypertensive rats (SHRs) was identified. Simvastatin-evoked relaxations of both depolarized and phenylephrine-precontracted arteries were independent of the presence of endothelium. This effect was inhibited by diltiazem and mevalonate, but not by the Rho-kinase inhibitor, Y-27632. Simvastatin prevented contraction induced by phenylephrine, calcium ionophore A-23187 and CaCl2 in Ca2+-free medium. Y-27632 decreased the effect of simvastatin. On the contrary, contraction induced by noradrenaline in Ca2+-free medium was not affected. These results suggest that simvastatin elicited an effect on vascular smooth muscle cells from SHRs that may involve blockade of extracellular calcium entry and decrease vascular contraction by affecting Rho-kinase.
Pérez-Guerrero
Concepción
C
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain.
Márquez-Martín
Ana
A
Herrera
Maria Dolores
MD
Marhuenda
Elisa
E
Alvarez de Sotomayor
María
M
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology; D002122:Calcium Chloride / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008798:Mevalonic Acid / Q000494:pharmacology; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D019821:Simvastatin / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000577:Amides; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D009125:Muscle Relaxants, Central; D011725:Pyridines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C108830:Y 27632; D010656:Phenylephrine; D011189:Potassium Chloride; D019821:Simvastatin; D004110:Diltiazem; D002122:Calcium Chloride; D008798:Mevalonic Acid; D009638:Norepinephrine; C000543:cyclopiazonic acid