Acute modulation of vasoconstrictor responses by pravastatin in small vessels.
Circ J
; 75(6): 1506-14, 2011.
Article
em En
| MEDLINE
| ID: mdl-21532183
ABSTRACT
BACKGROUND:
Statins have been shown to inhibit conduit vessel constrictor responses via the endothelial nitric oxide (NO) pathway. Clinical studies have implicated an effect in microvascular resistance vessels; however, direct effects of therapeutically relevant statin concentrations have not been examined. We examined the effect of acute pravastatin pretreatment on vasoconstrictor responsiveness of isolated rat mesenteric small vessels. METHODS ANDRESULTS:
Pravastatin (112 nmol/L) pretreatment for 60 min reduced both the potency and maximal constrictor responses to phenylephrine, thromboxane (U46619) and serotonin in small vessels. This effect was abolished by endothelial denudation, NO synthase (NOS) inhibition with N-ω-nitro-L-arginine methyl ester (L-NAME 300 µmol/L) and Akt inhibition (Akt1/2 kinase inhibitor 500 nmol/L), confirming an endothelium-dependent mechanism and implicating a NO-mediated effect via the Akt pathway. Maximal superoxide scavenging with polyethylene glycol-superoxide dismutase (PEG-SOD), 150 U/ml did not influence phenylephrine constrictor responses but potentiated pravastatin's effect, suggesting that the statin did not increase NO bioavailability merely via an antioxidant mechanism. In contrast, pravastatin did not affect endothelin-1 (ET-1) constrictor responses. However, after pre-incubation with a selective endothelin-B (ET(B)) receptor antagonist (BQ788 3 µmol/L) pravastatin inhibited ET-1 constriction, suggesting that its effect is via the same mechanistic pathway as the ET(B) receptor.CONCLUSIONS:
In small vessels, pravastatin inhibits constrictor responses by increasing endothelial NO bioavailability via the Akt pathway. Furthermore, ET(B) receptor blockade unmasks this effect in ET-1 constrictor responses.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasoconstrição
/
Pravastatina
/
Inibidores de Hidroximetilglutaril-CoA Redutases
/
Células Endoteliais
/
Artérias Mesentéricas
Limite:
Animals
Idioma:
En
Revista:
Circ J
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Austrália