Pressure overload-induced hypertrophy in transgenic mice selectively overexpressing AT^sub 2^ receptors in ventricular myocytes

The role of the angiotensin II type 2 (AT...) receptor in cardiac hypertrophy remains controversial. We studied the effects of AT... receptors on chronic pressure overload-induced cardiac hypertrophy in transgenic mice selectively overexpressing AT... receptors in ventricular myocytes. Left ventricular (LV) hypertrophy was induced by ascending aorta banding (AS). Transgenic mice overexpressing AT... (AT...TG-AS) and nontransgenic mice (NTG-AS) were studied after 70 days of aortic banding. Nonbanded NTG mice were used as controls. LV function was determined by catheterization via LV puncture and cardiac magnetic resonance imaging. LV myocyte diameter and interstitial collagen were determined by confocal microscopy. Atrial natriuretic polypeptide (ANP) and brain natriuretic peptide (BNP) were analyzed by Northern blot. Sarco(endo)plasmic reticulum Ca...-ATPase (SERCA)2, inducible nitric oxide synthase (iNOS), endothelial NOS, ERK1/2, p70S6K, Src-homology 2 domain-containing protein tyrosine phosphatase-1, and protein serine/threonine phosphatase 2A were analyzed by Western blot. LV myocyte diameter and collagen were significantly reduced in AT...TG-AS compared with NTG-AS mice. LV anterior and posterior wall thickness were not different between AT...TG-AS and NTG-AS mice. LV systolic and diastolic dimensions were significantly higher in AT2TG-AS than in NTG-AS mice. LV systolic pressure and end-diastolic pressure were lower in AT...TG-AS than in NTG-AS mice. ANP, BNP, and SERCA2 were not different between AT...TG-AS and NTG-AS mice. Phospholamban (PLB) and the PLB-to-SERCA2 ratio were significantly higher in AT...TG-AS than in NTG-AS mice. iNOS was higher in AT...TG-AS than in NTG-AS mice but not significantly different. Our results indicate that AT... receptor overexpression modified the pathological hypertrophic response to aortic banding in transgenic mice. (ProQuest: ... denotes formulae/symbols omitted.)