title: Plasma and tissue concentrations of proangiotensin-12 in rats treated with inhibitors of the renin-angiotensin system.
abstract: It has been suggested that proangiotensin-12 (proang-12), a novel angiotensin peptide recently discovered in rat tissues, may function as a component of the tissue renin-angiotensin system (RAS). To investigate the role of proang-12 in the production of angiotensin II (Ang II), we measured its plasma and tissue concentrations in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, with and without RAS inhibition. The 15-week-old male WKY and SHR rats were left untreated or were treated for 7 days with 30 mg kg(-1) per day losartan, an angiotensin receptor blocker, or with 20 mg kg(-1) per day imidapril, an angiotensin-converting enzyme (ACE) inhibitor. Both treatments increased renin activity and the concentrations of angiotensin I (Ang I) and Ang II in the plasma of WKY and SHR rats, but neither affected plasma proang-12 levels. In contrast to the comparatively low level of proang-12 seen in plasma, cardiac and renal levels of proang-12 were higher than those of Ang I and Ang II. In addition, despite activation of the RAS in the systemic circulation, tissue concentrations of proang-12 were significantly reduced following treatment with losartan or imidapril. Similar reductions were also observed in the tissue concentrations of Ang II in both strains, without a reduction in Ang I. These results suggest that tissue concentrations of proang-12 and Ang II are regulated independently of the systemic RAS in WKY and SHR rats, which is consistent with the notion that proang-12 is a component of only the tissue RAS.
authors: Department of Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. saya223@fc.miyazaki-u.ac.jp
authors: Sayaka
authors: S
authors: Nagata
authors: Johji
authors: J
authors: Kato
authors: Kenji
authors: K
authors: Kuwasako
authors: Maki
authors: M
authors: Asami
authors: Kazuo
authors: K
authors: Kitamura
mesh_terms: D000803:Angiotensin I / Q000097:blood / Q000378:metabolism; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D048289:Imidazolidines / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D048289:Imidazolidines; D010446:Peptide Fragments; C515557:proangiotensin-12, rat; D000808:Angiotensinogen; D000804:Angiotensin II; D000803:Angiotensin I; C065166:imidapril; D012083:Renin; D019808:Losartan