The positive inotropic effect of angiotensin II : Role of endothelin-1 and reactive oxygen species

Many effects believed to be because of angiotensin II (Ang II) are attributable to the action of endothelin (ET)-1, which is released/produced by Ang II. We investigated whether Ang II elicits its positive inotropic effect (PIE) by the action of endogenous ET-1, in addition to the role played by rea...

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Detalles Bibliográficos
Autores principales: Cingolani, Horacio Eugenio, Villa Abrille, María Celeste, Cornelli, Mariana, Nolly, Alejandro, Ennis, Irene Lucía, Garciarena, Carolina Denis, Suburo, Angela M., Torbidoni, Vanesa, Correa, María Verónica, Camilión de Hurtado, María Cristina, Aiello, Ernesto Alejandro
Formato: Articulo
Lenguaje:Inglés
Publicado: 2006
Materias:
Ciencias Médicas
Ion channels
Membranas
Oxidative stress
Receptores de Angiotensina
Angiotensina II
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/83462
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
Descripción
Sumario:Many effects believed to be because of angiotensin II (Ang II) are attributable to the action of endothelin (ET)-1, which is released/produced by Ang II. We investigated whether Ang II elicits its positive inotropic effect (PIE) by the action of endogenous ET-1, in addition to the role played by reactive oxygen species (ROS) in this mechanism. Cat cardiomyocytes were used for: (1) sarcomere shortening measurements; (2) ROS measurements by epifluorescence; (3) immunohistochemical staining for preproET-1, BigET-1, and ET-1; and (4) measurement of preproET-1 mRNA by RT-PCR. Cells were exposed to 1 nmol/L Ang II for 15 minutes. This low concentration of Ang II increases sarcomere shortening by 29.2±3.7% (P<0.05). This PIE was abrogated by Na+/H+ exchanger or Na+/Ca2+ exchanger reverse mode inhibition. The production of ROS increased in response to Ang II treatment (ΔROS respect to control: 68±15 fluorescence units; P<0.05). The Ang II-induced PIE and ROS production were blocked by the Ang II type 1 receptor blocker losartan, the nonselective ET-1 receptor blocker TAK044, the selective ETA receptor blocker BQ-123, or the ROS scavenger N-(2-mercapto-propionyl)glycine. Exogenous ET-1 (0.4 nmol/L) induced a similar PIE and increase in ROS production to those caused by Ang II. Immunostaining for preproET-1, BigET-1, and ET-I was positive in cardiomyocytes. The preproET-1 mRNA abundance increased from 100±4.6% in control to 241.9±39.9% in Ang II-treated cells (P<0.05). We conclude that the PIE after exposure to 1 nmol/L Ang II is due to endogenous ET-1 acting through the ETA receptor and triggering ROS production, Na+/H+ exchanger stimulation, and Na+/Ca2+ exchanger reverse mode activation.

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