title: Diabetes-induced increase of renal medullary hydrogen peroxide and urinary angiotensinogen is similar in normotensive and hypertensive rats.
abstract: OBJECTIVE
  Activation of renal renin-angiotensin system (RAS) and reactive oxygen species (ROS) are the main pathophysiological mechanisms associated with kidney injury both in diabetes and hypertension. However, the contribution to medullary damage when the two pathologies coexist has seldom been explored.
  
  
  METHODS
  Diabetes was induced with streptozotocin in twelve week-old male Wistar and spontaneously hypertensive rats (SHR) rats; controls received vehicle. Three weeks later, systolic blood pressure (SBP), plasma and urinary angiotensinogen (AGT), renal oxidative stress and metabolic status were evaluated.
  
  
  RESULTS
  SBP was higher in SHR-controls than in Wistar-controls (200±6 and 127±3mmHg, respectively) and decreased in SHR-diabetics but not in Wistar-diabetics (143±8 and 122±6mmHg, respectively). Renal medullary hydrogen peroxide (H2O2) production was similarly increased in diabetics (Wistar: 0.32±0.04 and 1.11±0.10nmol/mg protein, respectively; SHR: 0.40±0.05 and 0.90±0.14nmol/mg protein, respectively) and positively correlated with glycemia (Wistar: r=0.7166, SHR: r=0.7899, p<0.05) and urinary AGT excretion (Wistar: r=0.8333; SHR: r=0.8326, p<0.05). Cortical H2O2 production was higher in SHR-controls than in Wistar-controls (1.10±0.09 and 0.26±0.04nmol/mg protein, respectively) and diabetes induction decreased it in SHR (0.70±0.09nmol/mg protein). Diabetes increased urinary AGT excretion by more than 7-fold and decreased plasma AGT concentration by more than 1.5-fold in both strains.
  
  
  CONCLUSIONS
  Our results show that STZ-induced diabetes increases medullary H2O2 production and urinary AGT excretion with similar magnitude in normotensive and hypertensive animals. Reducing blood pressure attenuates hypertension-associated cortical damage but does not prevent medullary dysfunction.
authors.affiliation: Departamento de Farmacologia e Terapêutica, Faculdade de Medicina do Porto and MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal; Neurofarmacologia, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Patinha
authors.affiliation: Departamento de Farmacologia e Terapêutica, Faculdade de Medicina do Porto and MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Afonso
authors.affiliation: Departamento de Farmacologia e Terapêutica, Faculdade de Medicina do Porto and MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Sousa
authors.affiliation: Departamento de Farmacologia e Terapêutica, Faculdade de Medicina do Porto and MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal; Neurofarmacologia, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal; Laboratório de Farmacologia, Departamento de Ciências do Medicamento, Faculdade de Farmácia, REQUIMTE, Universidade do Porto, Porto, Portugal. Electronic address: mmorato@med.up.pt.
authors.forename: Manuela
authors.initials: M
authors.lastname: Morato
authors.affiliation: Departamento de Farmacologia e Terapêutica, Faculdade de Medicina do Porto and MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal; Neurofarmacologia, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Albino-Teixeira
mesh_terms: D000808:Angiotensinogen / Q000097:blood / Q000652:urine*; D000818:Animals; D001794:Blood Pressure; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D007672:Kidney Cortex / Q000473:pathology; D007679:Kidney Medulla / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012084:Renin-Angiotensin System; D013311:Streptozocin
chemical_list: D000808:Angiotensinogen; D013311:Streptozocin; D006861:Hydrogen Peroxide
keywords: hydrogen peroxide; hyperglycemia; kidney; renin-angiotensin system; systolic blood pressure