PT - JOURNAL ARTICLE AU - Katsutoshi Yayama AU - Miyuki Horii AU - Hiromi Hiyoshi AU - Masaoki Takano AU - Hiroshi Okamoto AU - Satomi Kagota AU - Masaru Kunitomo TI - Up-Regulation of Angiotensin II Type 2 Receptor in Rat Thoracic Aorta by Pressure-Overload AID - 10.1124/jpet.103.058420 DP - 2004 Feb 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 736--743 VI - 308 IP - 2 4099 - http://jpet.aspetjournals.org/content/308/2/736.short 4100 - http://jpet.aspetjournals.org/content/308/2/736.full SO - J Pharmacol Exp Ther2004 Feb 01; 308 AB - We have examined whether expression of angiotensin II (Ang II) type 1 (AT1) and/or type 2 (AT2) receptors are changed in thoracic aorta under pressure-overload by abdominal aortic banding in rats and determined whether their changes are accompanied by alteration in contractile response of thoracic aorta to Ang II. AT2 receptor mRNA levels determined by reverse transcription-polymerase chain reaction or quantitative real-time polymerase chain reaction were increased by about 300% in aortas 4, 7, 14, and 28 days after banding without changes in AT1 receptor mRNA levels. Contractile response of aortic rings to Ang II was decreased in thoracic aortas 7 days after banding, and AT2 receptor antagonist PD123319 (1-[[4-(dimethulamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate) (10–6 M) increased the Ang II responsiveness in pressure-loaded but not in sham rings. After removal of the endothelium or treatment with NG-nitro-l-arginine methyl ester (l-NAME), no differences were observed in Ang II responsiveness between sham and pressure-loaded rings. Either losartan (1 mg/kg/day i.p.) or candesartan (2 mg/kg/day p.o.) for 7 days after banding not only abolished the up-regulation of AT2 receptor mRNA in aortas but also recovered their Ang II responsiveness. Basal cGMP levels were 2 times higher in pressure-loaded than in sham rings; both levels were not affected by Ang II (10–7 M; 5 min), but greatly decreased by l-NAME (10–4 M, 30 min). These results suggest that pressure-overload induces the up-regulation of AT2 receptor expression in aortas via AT1 receptor and thereby negatively modulates the vasoconstrictor sensitivity to Ang II, probably mediated by the mechanisms independent of the nitric oxide-cGMP system. The American Society for Pharmacology and Experimental Therapeutics