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


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.
First Department of Medicine, Semmelweis University, and Molecular Genetic Research Group of the Hungarian Academy of Sciences, Budapest, Hungary.
Zoltán
Z
Lakó-Futó
István
I
Szokodi
Balázs
B
Sármán
Gábor
G
Földes
Heikki
H
Tokola
Mika
M
Ilves
Hanna
H
Leskinen
Olli
O
Vuolteenaho
Réka
R
Skoumal
Rudolf
R
deChâtel
Heikki
H
Ruskoaho
Miklós
M
Tóth
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D001794:Blood Pressure; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology / Q000503:physiopathology*; D016220:Fibroblast Growth Factor 1 / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D006339:Heart Rate; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D015918:Infusion Pumps, Implantable; D019808:Losartan / Q000494:pharmacology; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011725:Pyridines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D042461:Vascular Endothelial Growth Factor A; D016220:Fibroblast Growth Factor 1; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; C073402:PD 123319; D009320:Atrial Natriuretic Factor; D019808:Losartan