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(Circulation. 2003;108:2414.)
© 2003 American Heart Association, Inc.

Basic Science Reports

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, MD; István Szokodi, MD, PhD; Balázs Sármán, MD; Gábor Földes, MD, PhD; Heikki Tokola, MD; Mika Ilves, MSc; Hanna Leskinen, MD, PhD; Olli Vuolteenaho, MD, PhD; Réka Skoumal, MSc; Rudolf deChâtel, MD, PhD; Heikki Ruskoaho, MD, PhD; Miklós Tóth, MD, PhD

From the First Department of Medicine, Semmelweis University, and Molecular Genetic Research Group of the Hungarian Academy of Sciences (Z.L.-F., B.S., G.F., R.d.C., R.S., M.T.), Budapest, Hungary; the Heart Institute (I.S.), University of Pécs, Pécs, Hungary; and the Department of Pharmacology and Toxicology (I.S., H.T., H.L., H.R.) and the Department of Physiology (M.I., O.V.), Biocenter Oulu, University of Oulu, Oulu, Finland.

Correspondence to Heikki Ruskoaho, MD, PhD, Department of Pharmacology and Toxicology, University of Oulu, PO Box 5000, FIN-90014, Finland. E-mail heikki.ruskoaho{at}oulu.fi

Received December 6, 2002; de novo received May 22, 2003; revision received July 11, 2003; accepted July 11, 2003.

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 -actin and ß-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.

Key Words: angiotensin • receptors • hypertrophy • growth substances • natriuretic peptides

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