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(Hypertension. 2006;47:727.)
© 2006 American Heart Association, Inc.

Original Articles

The Positive Inotropic Effect of Angiotensin II

Role of Endothelin-1 and Reactive Oxygen Species

Horacio E. Cingolani; María C. Villa-Abrille; Mariana Cornelli; Alejandro Nolly; Irene L. Ennis; Carolina Garciarena; Angela M. Suburo; Vanesa Torbidoni; María V. Correa; María C. Camiliónde Hurtado; Ernesto A. Aiello

From the Centro de Investigaciones Cardiovasculares (H.E.C., M.C.V.-A., M.C., A.N., I.L.E., C.G., M.V.C., M.C.C.d.H., E.A.A.), Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata; and Facultad de Ciencias Biomédicas (A.M.S., V.T.), Universidad Austral, Pilar, Buenos Aires, Argentina.

Correspondence to Horacio E. Cingolani, Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120 (1900) La Plata, Argentina. E-mail cimes{at}infovia.com.ar

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 (ROS 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 ET_A 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-1 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 ET_A receptor and triggering ROS production, Na⁺/H⁺ exchanger stimulation, and Na⁺/Ca²⁺ exchanger reverse mode activation.

Key Words: membranes • ion channels • oxidative stress • receptors, angiotensin

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