title: Apoptosis and NFkappaB activation are simultaneously induced in renal tubulointerstitium in experimental hypertension.
abstract: BACKGROUND
  Oxidative stress is known to induce apoptosis and activation of pro-inflammatory transcription factor nuclear factor kappa B (NFkappaB), which are biologic effects that may play a role in the renal damage associated with arterial hypertension. We investigated if increased apoptosis and NFkappaB activation were present in experimental models of hypertension.
  
  
  METHODS
  Sprague-Dawley rats fed with regular rodent chow and free access to water were studied. The Ang II group (N = 6) received 435 ng/kg/min of angiotensin II during 2 weeks by subcutaneous minipumps. The l-NAME group (N = 5) received Nomega-nitro-l-arginine-methyl-ester (l-NAME) in the drinking water (70 mg/100 mL) for 3 weeks. The control group consisted of 6 rats. Systolic blood pressure (tail cuff plethysmography), serum creatinine, and proteinuria were determined weekly. Kidneys were examined for superoxide-positive cells (histochemistry) and for apoptosis [terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick-end labeling (TUNEL)-positive cells], proliferation [proliferating cell nuclear antigen (PCNA)-positive cells), and activation of NFkappaB (p65 subunit) with the appropriate antibodies.
  
  
  RESULTS
  As expected, hypertension developed in experimental groups. Tubulointerstitial superoxide-positive cells were increased 7 times (P < 0.001), TUNEL-positive cells were increased 3 to 4 times (P < 0.001), PCNA-positive cells were increased 20 to 30 times (P < 0.001), and NFkappaB activation was increased 4 to 5 times (P < 0.001) in the experimental groups. NFkappaB expression correlated with the number of interstitial lymphocytes (r = 0.667, P < 0.01) and macrophages (r = 0.835, P < 0.001).
  
  
  CONCLUSIONS
  Angiotensin II infusion and l-NAME administration induce oxidative stress and increased apoptosis and activation of the transcription factor NFkappaB. These effects may participate in the development of progressive renal injury resulting from uncontrolled hypertension
authors.affiliation: Renal Service and Laboratory, Hospital Universitario, FUNDACITE-Zulia, Maracaibo, Venezuela.
authors.forename: Yasmir
authors.initials: Y
authors.lastname: Quiroz
authors.forename: Janaury
authors.initials: J
authors.lastname: Bravo
authors.forename: Jaime
authors.initials: J
authors.lastname: Herrera-Acosta
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rodríguez-Iturbe
mesh_terms: D000804:Angiotensin II; D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure; D004791:Enzyme Inhibitors; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D051381:Rats; D017207:Rats, Sprague-Dawley; D051996:Transcription Factor RelA
chemical_list: D004791:Enzyme Inhibitors; D016328:NF-kappa B; D051996:Transcription Factor RelA; D000804:Angiotensin II; D019331:NG-Nitroarginine Methyl Ester