Evidence for a Functional Role of Angiotensin II Type 2 Receptor in the Cardiac Hypertrophic Process in Vivo in the Rat Heart

Zoltán Lakó-Futó, István Szokodi, Balázs Sármán, Gábor Földes, Heikki Tokola, Mika Ilves, Hanna Leskinen, Olli Vuolteenaho, Réka Skoumal, Rudolf DeChâtel, Heikki Ruskoaho, Miklós Tóth

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Abstract

Background - The precise function of angiotensin II type 2 receptor (AT2-R) in the mammalian heart in vivo is unknown. Here, we investigated the role of AT2-R in cardiac pressure overload. Methods and Results - Rats were infused with vehicle, angiotensin II (Ang II), PD123319 (an AT2-R antagonist), or the combination of Ang II and PD123319 via subcutaneously implanted osmotic minipumps for 12 or 72 hours, Ang II-induced increases in mean arterial pressure, left ventricular weight/body weight ratio, and elevation of skeletal α-actin and β-myosin heavy chain mRNA levels were not altered by PD123319. In contrast, AT2-R blockade resulted in a marked increase in the gene expression of c-fos, endothelin-1, and insulin-like growth factor-1 in Ang II-induced hypertension. In parallel, Ang II-stimulated mRNA and protein expression of atrial natriuretic peptide were significantly augmented by AT2-R blockade. Moreover, PD123319 markedly increased the synthesis of B-type natriuretic peptide. Furthermore, the expression of vascular endothelial growth factor and fibroblast growth factor-1 was downregulated by Ang II only in the presence of AT2-R blockade. Conclusions - Our results provide evidence that AT2-R plays a functional role in the cardiac hypertrophic process in vivo by selectively regulating the expression of growth-promoting and growth-inhibiting factors.

Original languageEnglish
Pages (from-to)2414-2422
Number of pages9
JournalCirculation
Volume108
Issue number19
DOIs
Publication statusPublished - Nov 11 2003

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Keywords

  • Angiotensin
  • Growth substances
  • Hypertrophy
  • Natriuretic peptides
  • Receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Lakó-Futó, Z., Szokodi, I., Sármán, B., Földes, G., Tokola, H., Ilves, M., Leskinen, H., Vuolteenaho, O., Skoumal, R., DeChâtel, R., Ruskoaho, H., & Tóth, M. (2003). Evidence for a Functional Role of Angiotensin II Type 2 Receptor in the Cardiac Hypertrophic Process in Vivo in the Rat Heart. Circulation, 108(19), 2414-2422. https://doi.org/10.1161/01.CIR.0000093193.63314.D9