title: Chronic treatment with atrial natriuretic peptide in spontaneously hypertensive rats: beneficial renal effects and sex differences.
abstract: OBJECTIVE
  The aim of this study was to investigate the effects of chronic treatment with atrial natriuretic peptide (ANP) on renal function, nitric oxide (NO) system, oxidative stress, collagen content and apoptosis in kidneys of spontaneously hypertensive rats (SHR), as well as sex-related differences in the response to the treatment.
  
  
  METHODS
  10 week-old male and female SHR were infused with ANP (100 ng/h/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). Systolic blood pressure (SBP) was recorded and diuresis and natriuresis were determined. After treatment, renal NO synthase (NOS) activity and eNOS expression were evaluated. Thiobarbituric acid-reactive substances (TBARS), glutathione concentration and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were determined in the kidney. Collagen was identified in renal slices by Sirius red staining and apoptosis by Tunel assay.
  
  
  RESULTS
  Female SHR showed lower SBP, oxidative stress, collagen content and apoptosis in kidney, and higher renal NOS activity and eNOS protein content, than males. ANP lowered SBP, increased diuresis, natriuresis, renal NOS activity and eNOS expression in both sexes. Renal response to ANP was more marked in females than in males. In kidney, ANP reduced TBARS, renal collagen content and apoptosis, and increased glutathione concentration and activity of GPx and SOD enzymes in both sexes.
  
  
  CONCLUSIONS
  Female SHR exhibited less organ damage than males. Chronic ANP treatment would ameliorate hypertension and end-organ damage in the kidney by reducing oxidative stress, increasing NO-system activity, and diminishing collagen content and apoptosis, in both sexes.
authors.affiliation: Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IQUIMEFA-CONICET, Junín 956, piso 7, 1113 Ciudad de Buenos Aires, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Romero
authors.affiliation: Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IQUIMEFA-CONICET, Junín 956, piso 7, 1113 Ciudad de Buenos Aires, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Caniffi
authors.affiliation: Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IQUIMEFA-CONICET, Junín 956, piso 7, 1113 Ciudad de Buenos Aires, Argentina.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Bouchet
authors.affiliation: Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IQUIMEFA-CONICET, Junín 956, piso 7, 1113 Ciudad de Buenos Aires, Argentina.
authors.forename: María A
authors.initials: MA
authors.lastname: Costa
authors.affiliation: Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IQUIMEFA-CONICET, Junín 956, piso 7, 1113 Ciudad de Buenos Aires, Argentina.
authors.forename: Rosana
authors.initials: R
authors.lastname: Elesgaray
authors.affiliation: Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IQUIMEFA-CONICET, Junín 956, piso 7, 1113 Ciudad de Buenos Aires, Argentina.
authors.forename: Cristina
authors.initials: C
authors.lastname: Arranz
authors.affiliation: Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IQUIMEFA-CONICET, Junín 956, piso 7, 1113 Ciudad de Buenos Aires, Argentina.
authors.forename: Analía L
authors.initials: AL
authors.lastname: Tomat
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D005260:Female; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012737:Sex Factors
chemical_list: D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D019001:Nitric Oxide Synthase