Evidence for a functional role of angiotensin II type 2 receptor in the cardiac hypertrophic process in vivo in the rat heart.

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 alpha-actin and beta-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.

• Authors: 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
• Journal: Circulation (Circulation) Vol. 108 Issue 19 Pg. 2414-22 (Nov 11 2003) ISSN: 1524-4539 [Electronic] United States
• PMID: 14568903 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Angiotensin II Type 2 Receptor Blockers
• Imidazoles
• Proto-Oncogene Proteins c-fos
• Pyridines
• RNA, Messenger
• Receptor, Angiotensin, Type 2
• Vascular Endothelial Growth Factor A
• Fibroblast Growth Factor 1
• Angiotensin II
• Natriuretic Peptide, Brain
• PD 123319
• Atrial Natriuretic Factor
• Losartan

Topics

• Angiotensin II (administration & dosage, pharmacology, physiology)
• Angiotensin II Type 1 Receptor Blockers
• Angiotensin II Type 2 Receptor Blockers
• Animals
• Atrial Natriuretic Factor (biosynthesis, genetics)
• Blood Pressure
• Cardiomyopathy, Hypertrophic (etiology, physiopathology)
• Fibroblast Growth Factor 1 (biosynthesis, genetics)
• Gene Expression Regulation (drug effects)
• Genes, fos
• Heart Rate
• Hypertension (chemically induced, physiopathology)
• Imidazoles (pharmacology)
• Infusion Pumps, Implantable
• Losartan (pharmacology)
• Male
• Natriuretic Peptide, Brain (biosynthesis, genetics)
• Proto-Oncogene Proteins c-fos (biosynthesis)
• Pyridines (pharmacology)
• RNA, Messenger (biosynthesis)
• Rats
• Rats, Sprague-Dawley
• Receptor, Angiotensin, Type 2 (physiology)
• Vascular Endothelial Growth Factor A (biosynthesis, genetics)