title: Increased angiotensinogen expression, urinary angiotensinogen excretion, and tissue injury in nonclipped kidneys of two-kidney, one-clip hypertensive rats.
abstract: In angiotensin II (ANG II)-dependent hypertension, there is an angiotensin type 1 receptor-dependent amplification mechanism enhancing intrarenal angiotensinogen (AGT) formation and secretion in the tubular fluid. To evaluate the role of increased arterial pressure, AGT mRNA, protein expression, and urinary AGT (uAGT) excretion and tissue injury were assessed in both kidneys of two-kidney, one-clip Sprague-Dawley hypertensive rats subjected to left renal arterial clipping (0.25-mm gap). By 18-21 days, systolic arterial pressure increased to 180 ± 3 mmHg, and uAGT increased. Water intake, body weights, 24-h urine volumes, and sodium excretion were similar. In separate measurements of renal function in anesthetized rats, renal plasma flow and glomerular filtration rate were similar in clipped and nonclipped kidneys and not different from those in sham rats, indicating that the perfusion pressure to the clipped kidneys remained within the autoregulatory range. The nonclipped kidneys exhibited increased urine flow and sodium excretion. The uAGT excretion was significantly greater in nonclipped kidneys compared with clipped and sham kidneys. AGT mRNA was 2.15-fold greater in the nonclipped kidneys compared with sham (1.0 ± 0.1) or clipped (0.98 ± 0.15) kidneys. AGT protein levels were also greater in the nonclipped kidneys. The nonclipped kidneys exhibited greater glomerular expansion and immune cell infiltration, medullary fibrosis, and cellular proliferation than the clipped kidneys. Because both kidneys have elevated ANG II levels, the greater tissue injury in the nonclipped kidneys indicates that an increased arterial pressure synergizes with increased intrarenal ANG II to stimulate AGT production and exert greater renal injury.
authors.affiliation: Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana wshao@tulane.edu.
authors.forename: Weijian
authors.initials: W
authors.lastname: Shao
authors.affiliation: Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Miyata
authors.affiliation: Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Akemi
authors.initials: A
authors.lastname: Katsurada
authors.affiliation: Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Ryousuke
authors.identifier: 0000-0001-6505-9722
authors.initials: R
authors.lastname: Satou
authors.affiliation: Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Dale M
authors.initials: DM
authors.lastname: Seth
authors.affiliation: Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Carla B
authors.initials: CB
authors.lastname: Rosales
authors.affiliation: Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Minolfa C
authors.initials: MC
authors.lastname: Prieto
authors.affiliation: Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Mitchell
authors.affiliation: Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000808:Angiotensinogen / Q000096:biosynthesis* / Q000652:urine*; D000818:Animals; D062186:Arterial Pressure; D001835:Body Weight; D004326:Drinking; D005355:Fibrosis; D006978:Hypertension, Renovascular / Q000473:pathology* / Q000652:urine*; D007111:Immunity, Cellular; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D007679:Kidney Medulla / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine
chemical_list: D012333:RNA, Messenger; D000808:Angiotensinogen; D012964:Sodium
keywords: glomerular filtration rate; intrarenal angiotensinogen messenger ribonucleic acid expression; renal hemodynamics; renal injury; renin-angiotensin system