Localization of the novel angiotensin peptide, angiotensin-(1-12), in heart and kidney of hypertensive and normotensive rats.
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.
Jessup
Jewell A
JA
Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. jjessup@wfubmc.edu
Trask
Aaron J
AJ
Chappell
Mark C
MC
Nagata
Sayaka
S
Kato
Johji
J
Kitamura
Kazuo
K
Ferrario
Carlos M
CM
D000808:Angiotensinogen / Q000032:analysis* / Q000276:immunology; D000818:Animals; D000918:Antibody Specificity; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D007684:Kidney Tubules / Q000737:chemistry*; D008297:Male; D009206:Myocardium / Q000737:chemistry*; D032383:Myocytes, Cardiac / Q000737:chemistry; D010446:Peptide Fragments / Q000032:analysis* / Q000276:immunology; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D010446:Peptide Fragments; C515557:proangiotensin-12, rat; D000808:Angiotensinogen