{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T13:03:04Z","timestamp":1775048584086,"version":"3.50.1"},"reference-count":40,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2016,4,15]]},"abstract":"<jats:p>Angiotensin-(1\u201312) [ANG-(1\u201312)] is processed into ANG II by chymase in rodent and human heart tissue. Differences in the amino acid sequence of rat and human ANG-(1\u201312) render the human angiotensinogen (hAGT) protein refractory to cleavage by renin. We used transgenic rats harboring the hAGT gene [TGR(hAGT)L1623] to assess the non-renin-dependent effects of increased hAGT expression on heart function and arterial pressure. Compared with Sprague-Dawley (SD) control rats ( n = 11), male homozygous TGR(hAGT)L1623 ( n = 9) demonstrated sustained daytime and nighttime hypertension associated with no changes in heart rate but increased heart rate lability. Increased heart weight\/tibial length ratio and echocardiographic indexes of cardiac hypertrophy were associated with modest reduction of systolic function in hAGT rats. Robust human ANG-(1\u201312) immunofluorescence within myocytes of TGR(hAGT)L1623 rats was associated with a fourfold increase in cardiac ANG II content. Chymase enzymatic activity, using the rat or human ANG-(1\u201312) as a substrate, was not different in the cardiac tissue of SD and hAGT rats. Since both cardiac angiotensin-converting enzyme (ACE) and ACE2 activities were not different among the two strains, the changes in cardiac structure and function, blood pressure, and left ventricular ANG II content might be a product of an increased cardiac expression of ANG II generated through a non-renin-dependent mechanism. The data also underscore the existence in the rat of alternate enzymes capable of acting on hAGT protein. Homozygous transgenic rats expressing the hAGT gene represent a novel tool to investigate the contribution of human relevant renin-independent cardiac ANG II formation and function.<\/jats:p>","DOI":"10.1152\/ajpheart.00833.2015","type":"journal-article","created":{"date-parts":[[2016,2,13]],"date-time":"2016-02-13T12:33:54Z","timestamp":1455366834000},"page":"H995-H1002","source":"Crossref","is-referenced-by-count":24,"title":["Cardiac angiotensin-(1\u201312) expression and systemic hypertension in rats expressing the human angiotensinogen gene"],"prefix":"10.1152","volume":"310","author":[{"given":"Carlos M.","family":"Ferrario","sequence":"first","affiliation":[{"name":"Department of Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina;"},{"name":"Departments of Medicine-Nephrology and Physiology-Pharmacology, Wake Forest School of Medicine, Winston Salem, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"VonCannon","sequence":"additional","affiliation":[{"name":"Department of Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina;"},{"name":"Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston Salem, North Carolina;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarfaraz","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston Salem, North Carolina;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Bader","sequence":"additional","affiliation":[{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine (MDC), Berlin, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis J.","family":"Dell'Italia","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, University of Alabama at Birmingham and Department of Veterans Affairs, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leanne","family":"Groban","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston Salem, North Carolina;"},{"name":"Department of Anesthesiology, Wake Forest School of Medicine, Winston Salem, North Carolina; 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