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Experimental Hypertension is Associated with Differential Expression of Angiotensin‐(1–12) in Heart of Hypertensive and Normotensive Rats
Author(s) -
Jessup Jewell A,
Habibi Javad,
Trask Aaron J.,
Chappell Mark C.,
Nagata Sayaka,
Kato Johji,
Kitamura Kazuo,
Sowers James R.,
Ferrario Carlos M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1210.20
Subject(s) - medicine , renin–angiotensin system , endocrinology , angiotensin ii , spontaneously hypertensive rat , myocyte , chemistry , blood pressure
Low expression of angiotensinogen in the heart has been construed as indicating a circulating uptake mechanism to explain the local effects of angiotensin II in the tissue. The recent identification of angiotensin‐12 [Ang‐(1–12)] and our localization of the propeptide in cardiac myocytes led us to hypothesize that Ang‐(1–12) may be an alternate substrate for local angiotensin production. Immunolocalization of Ang‐(1–12) in the heart of SHR and WKY rats [11 weeks, n = 8], revealed robust and mottled Ang‐(1–12) staining found predominantly in ventricular myocytes with less, but distinct staining found in the medial layer of intra‐coronary arteries and vascular endothelium. Quantitative analysis of the stained sections, captured using laser confocal microscopy, demonstrated that the average cardiac grayscale staining intensity of the fluorescent signal was 3‐fold higher (P < 0.0001) in SHR compared to WKY paralleling tissue content measurements of Ang‐(1–12) which demonstrated a 47% higher (P < 0.05) content of the propeptide in the heart of SHR compared to WKY. These new findings suggest that Ang‐(1–12) functions as a preprohormone for tissue‐specific renin‐angiotensin systems. Furthermore, the differential manifestation between the normo‐ and hypertensive models is indicative of a role for Ang‐(1–12) in the evolution of a genetic form of hypertension. Funding provided by NIH (HL‐51952).