Erythropoietin Reverses Sepsis-Induced Vasoplegia to Norepinephrine Through Preservation of α1D-Adrenoceptor mRNA Expression and Inhibition of GRK2-Mediated Desensitization in Mouse Aorta.
J Cardiovasc Pharmacol Ther
; 21(1): 100-13, 2016 Jan.
Article
en En
| MEDLINE
| ID: mdl-26025460
ABSTRACT
We investigated the effect of erythropoietin (EPO) posttreatment on survival time and vascular functions in a mouse model of sepsis. Sepsis was induced by cecal ligation and puncture. After 20 ± 2 hours of sepsis, thoracic aorta was isolated for assessing its reactivity to norepinephrine (NE) and acetylcholine (ACh). We also measured the tissue nitric oxide (NO) level, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), G protein-coupled receptor kinase 2 (GRK2), and α1D adrenoceptor messenger RNA (mRNA)/protein expression. In septic mice, EPO moderately improved the survival time from 19.68 ± 0.75 to 34.7 ± 3.2 hours. Sepsis significantly decreased the aortic contractile response to NE along with reduced α1D mRNA and protein expression. Erythropoietin significantly preserved the α1D receptor expression and restored NE-induced contractions to control levels in septic mice. Further, it attenuated the aortic α1D receptor desensitization in sepsis which was evident from reduced GRK2 mRNA expression. Accordingly, a selective GRK2 inhibitor markedly restored the contractile responses to NE in sepsis. Erythropoietin treatment attenuated iNOS mRNA expression and iNOS-induced overproduction of NO, but improved endothelium-dependent relaxation to ACh associated with increased eNOS mRNA expression. In conclusion, EPO seems to reverse sepsis-induced vasoplegia to NE through the preservation of α1D adrenoceptor mRNA/protein expression, inhibition of GRK2-mediated desensitization, and attenuation of NO overproduction in the mouse aorta.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Aorta Torácica
/
Vasoconstrictores
/
ARN Mensajero
/
Norepinefrina
/
Eritropoyetina
/
Receptores Adrenérgicos alfa 1
/
Agonistas alfa-Adrenérgicos
/
Sepsis
/
Quinasa 2 del Receptor Acoplado a Proteína-G
/
Vasoplejía
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
J Cardiovasc Pharmacol Ther
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
FARMACOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
India