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. Camilión De Hurtado, Ernesto A. Aiello

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)727-734
Number of pages8
JournalHypertension
Volume47
Issue number4
DOIs
StatePublished - Apr 2006

Keywords

  • Ion channels
  • Membranes
  • Oxidative stress
  • Receptors, angiotensin

ASJC Scopus subject areas

  • Internal Medicine

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