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Am J Physiol Heart Circ Physiol (April 11, 2008). doi:10.1152/ajpheart.91521.2007
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Submitted on December 26, 2007
Revised on April 2, 2008
Accepted on April 3, 2008

Localization of the Novel Angiotensin Peptide, Angiotensin-12 [Ang-(1-12)], in Heart and Kidney of Hypertensive and Normotensive Rats

Jewell A Jessup1*, Aaron J. Trask1, Mark C. Chappell1, Sayaka Nagata, Johji Kato, Kazuo Kitamura2, and Carlos M Ferrario1

1 Wake Forest University School of Medicine
2 First Department of Internal Medicine, Miyazaki

* To whom correspondence should be addressed. E-mail: jjessup{at}wfubmc.edu.

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 week old SHR and WKY rats [n = 14] were stained with purified antibodies directed to the C-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 intra-coronary 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. Pre-adsorption 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 to WKY (P < 0.05). In contrast, renal angiotensin-(1-12) levels were 16.5% lower in SHR compared to the WKY (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 rats. 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.




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