title: Chronic direct renin inhibition with aliskiren prevents the development of hypertension in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent hypertension.
abstract: BACKGROUND
  This study was performed to determine whether chronic direct renin inhibition can prevent the development of slowly progressive angiotensin (ANG) II-dependent hypertension and the associated derangements in renal function in Cyplal-Ren2 transgenic rats with inducible expression of the Ren2 gene.
  
  
  METHODS
  Male Cyplal-Ren2 rats (n = 6) were fed a normal diet containing 0.15% indole-3-carbinol (I3C) for 16 days to induce slowly progressive ANG II-dependent hypertension. Conscious systolic blood pressure was measured daily using tail-cuff plethysmography. The rats were then anesthetized with pentobarbital sodium and surgically prepared for the measurement of mean arterial pressure (MAP) and renal hemodynamics and excretory function.
  
  
  RESULTS
  In rats induced with I3C, systolic blood pressure increased by day 3 (130 ± 7-160 ± 5 mm Hg, P < 0.01) and continued to increase to 191 ± 6 mm Hg (P < 0.001) by day 16. In a separate group of rats (n = 6), chronic administration of the direct renin inhibitor, aliskiren (30 mg/kg/d, sc), prevented the development of hypertension (113 ± 5 versus 114 ± 5 mm Hg, not significant). Rats treated with aliskiren exhibited significantly lower mean arterial pressure (138 ± 4 versus 201 ± 6 mm Hg, P < 0.001), renal vascular resistance (23 ± 4 versus 38 ± 3 mm Hg/mL/min · g, P < 0.01), urine flow (17.6 ± 1.4 versus 25.1 ± 2.9 μL/min, P < 0.05) and urinary sodium excretion (1.11 ± 0.32 versus 2.35 ± 0.28 μEq/min, P < 0.05) and higher renal plasma flow (4.22 ± 0.23 versus 2.56 ± 0.21 mL/min · g, P < 0.01) and glomerular filtration rate (1.19 ± 0.07 versus 0.78 ± 0.08 mL/min · g, P< 0.01), compared with induced rats not treated chronically with aliskiren.
  
  
  CONCLUSIONS
  The present findings demonstrate that chronic direct renin inhibition with aliskiren prevents the development of ANG II-dependent hypertension and the associated derangements in renal hemodynamics and excretory function in Cyplal-Ren2 transgenic rats.
authors.affiliation: Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Lily
authors.initials: L
authors.lastname: Huang
authors.forename: Catherine G
authors.initials: CG
authors.lastname: Howard
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Mitchell
mesh_terms: D000577:Amides / Q000494:pharmacology* / Q000627:therapeutic use; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D005650:Fumarates / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D051381:Rats; D055647:Rats, Transgenic; D012083:Renin / Q000235:genetics / Q000378:metabolism; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000804:Angiotensin II; D019363:Cytochrome P-450 CYP1A1; D005650:Fumarates; D012083:Renin; D000092502:Renin Inhibitors; C535029:Ren2 protein, rat; C446481:aliskiren