AKT participates in endothelial dysfunction in hypertension

Guido Iaccarino, Michele Ciccarelli, Daniela Sorriento, Ersilia Cipolletta, Vincenzo Cerullo, Gianni Luigi Iovino, Alessandro Paudice, Andrea Elia, Gaetano Santulli, Alfonso Campanile, Oreste Arcucci, Lucio Pastore, Francesco Salvatore, Gianluigi Condorelli, Bruno Trimarco

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Background - In hypertension, reduced nitric oxide production and blunted endothelial vasorelaxation are observed. It was recently reported that AKT phosphorylates and activates endothelial nitric oxide synthase and that impaired kinase activity may be involved in endothelial dysfunction. Methods and Results - To identify the physiological role of the kinase in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), we used adenoviral vectors to transfer the human AKTI gene selectively to the common carotid endothelium. In vitro, endothelial vasorelaxations to acetylcholine, isoproterenol, and insulin were blunted in control carotids from SHR compared with WKY rats, and human AKT1 overexpression corrected these responses. Similarly, blood flow assessed in vivo by Doppler ultrasound was reduced in SHR compared with WKY carotids and normalized after AKT1 gene transfer. In primary cultured endothelial cells, we evaluated AKT phosphorylation, activity, and compartmentalization and observed a mislocalization of the kinase in SHR. Conclusions - We conclude that AKT participates in the settings of endothelial dysfunction in SHR rats by impaired membrane localization. Our data suggest that AKT is involved in endothelium dysfunction in hypertension.

Original languageEnglish (US)
Pages (from-to)2587-2593
Number of pages7
JournalCirculation
Volume109
Issue number21
DOIs
StatePublished - Jun 1 2004
Externally publishedYes

Keywords

  • Endothelium
  • Gene therapy
  • Hypertension
  • Signal transduction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Iaccarino, G., Ciccarelli, M., Sorriento, D., Cipolletta, E., Cerullo, V., Iovino, G. L., Paudice, A., Elia, A., Santulli, G., Campanile, A., Arcucci, O., Pastore, L., Salvatore, F., Condorelli, G., & Trimarco, B. (2004). AKT participates in endothelial dysfunction in hypertension. Circulation, 109(21), 2587-2593. https://doi.org/10.1161/01.CIR.0000129768.35536.FA