title: Renal outcome in equipotent antihypertensive treatment with telmisartan, ramipril and in combination in SHR-SP rats.
abstract: BACKGROUND
  The ONTARGET trial revealed an association of ACEI/ARB combination treatment (telmisartan and ramipril) with adverse renal outcome versus respective monotherapy; preclinical evidence regarding renal outcome in ACEI/ARB combination treatment is scarce.
  
  
  METHODS
  Spontaneously hypertensive stroke prone rats (SHR-SP) rats on a salt-rich diet were randomly allocated to 4 groups: SHR (untreated, n = 24), SHR + telmisartan (SHR-T, 2.39 +/- 0.69 mg/kg bw; n = 27), SHR + ramipril (SHR-R, 6.28 +/- 3.48 mg/kg bw; n = 27) and combination treatment (SHR-TR, 0.51 +/- 0.14 mg/kg bw; same dose for telmisartan and ramipril; n = 26). Study duration was 12 weeks, blood pressure was assessed weekly and doses were adjusted to maintain equal blood pressure. Finally, blood and urine samples were obtained and kidneys were harvested for histological studies.
  
  
  RESULTS
  Blood pressure in untreated rats rose to a maximum of 239 mmHg, whereas in all treatment groups it remained stable between 140 and 150 mmHg. Mortality was 50% in the untreated group, whereas all treatment groups survived completely. Renal function--as indicated by plasma urea and cystatin c--was significantly worse in SHR-TR animals compared to all other groups. With plasma creatinine a similar trend was observed. All treatment options significantly decreased albuminuria. Renal glomerulosclerosis was decreased by monotherapy, whereas combination therapy failed to have a significant effect. Interstitial fibrosis was decreased to a similar extent by all treatment options.
  
  
  CONCLUSIONS
  ACEI/ARB combination treatment failed to render significant additional benefits on renal outcome in hypertensive rats when compared to monotherapy. Instead our data indicate that dual RAAS blockade might have an adverse effect on kidney function and histology when compared to monotherapy in salt-loaded SHR-SP.
authors.affiliation: Center for Cardiovascular Research (CCR)/Institute of Pharmacology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schmerbach
authors.forename: P
authors.initials: P
authors.lastname: Kalk
authors.forename: C
authors.initials: C
authors.lastname: Wengenmayer
authors.forename: K
authors.initials: K
authors.lastname: Lucht
authors.forename: T
authors.initials: T
authors.lastname: Unger
authors.forename: B
authors.initials: B
authors.lastname: Hocher
authors.forename: C
authors.initials: C
authors.lastname: Thoene-Reineke
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D001565:Benzoates / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure; D001835:Body Weight; D004359:Drug Therapy, Combination; D007677:Kidney Function Tests; D009929:Organ Size; D017257:Ramipril / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D015996:Survival Rate; D000077333:Telmisartan
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D017257:Ramipril; D000077333:Telmisartan