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Am J Physiol Heart Circ Physiol 294: H2614-H2618, 2008. First published April 11, 2008; doi:10.1152/ajpheart.91521.2007
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Localization of the novel angiotensin peptide, angiotensin-(1-12), in heart and kidney of hypertensive and normotensive rats

Jewell A. Jessup,1 Aaron J. Trask,1 Mark C. Chappell,1 Sayaka Nagata,2 Johji Kato,2 Kazuo Kitamura,2 and Carlos M. Ferrario1

1Hypertension and Vascular Research Center and Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; and 2Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan

Submitted 26 December 2007 ; accepted in final form 3 April 2008

A low expression of angiotensinogen in the heart has been construed as indicating a circulating uptake mechanism to explain the local effects of angiotensin II on tissues. The recent identification of angiotensin-(1-12) in an array of rat organs suggests this propeptide may be an alternate substrate for local angiotensin production. To test this hypothesis, tissues from 11-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (n = 14) were stained with purified antibodies directed to the COOH terminus of angiotensin-(1-12). Robust angiotensin-(1-12) staining was predominantly found in ventricular myocytes with less staining found in the medial layer of intracoronary arteries and vascular endothelium. In addition, angiotensin-(1-12) immunoreactivity was present in the proximal, distal, and collecting renal tubules within the deep cortical and outer medullary zones in both strains. Preadsorption of the antibody with angiotensin-(1-12) abolished staining in both tissues. Corresponding tissue measurements by radioimmunoassay showed 47% higher levels of angiotensin-(1-12) in the heart of SHR compared with WKY rats (P < 0.05). In contrast, renal angiotensin-(1-12) levels were 16.5% lower in SHR compared with the WKY rats (P < 0.05). This study shows for first time the localization of angiotensin-(1-12) in both cardiac myocytes and renal tubular components of WKY and SHR. In addition, we show that increased cardiac angiotensin-(1-12) concentrations in SHR is associated with a small, but statistically significant, reduction in renal angiotensin-(1-12) levels.

angiotensinogen; angiotensin I; angiotensin II; hypertension; renin


Address for reprint requests and other correspondence: J. A. Jessup, The Hypertension and Vascular Research Ctr., Wake Forest Univ. School of Medicine, 1 Medical Center Blvd., Winston-Salem, NC 27157 (e-mail: jjessup{at}wfubmc.edu)




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