title: Transient prehypertensive treatment in spontaneously hypertensive rats: a comparison of spironolactone and losartan regarding long-term blood pressure and target organ damage.
abstract: OBJECTIVE
  We previously demonstrated that when the renin-angiotensin system (RAS) is transiently blocked by an angiotensin receptor blocker (ARB) in young spontaneously hypertensive rats (SHR), this results in a prolonged blood pressure decrease and protection against target organ damage. Aldosterone is an essential hormone in the RAS, and contributes to pathologic remodeling. Thus, part of the protective effects of the ARB may be due to inhibition of aldosterone-mediated effects. To test this hypothesis, in young SHR, we compared the effectiveness of transient treatment with the mineralocorticoid receptor blocker spironolactone with those obtained by the ARB losartan.
  
  
  METHODS
  SHR were transiently (i.e. between 4-8 weeks of age) treated with spironolactone (SHR-Spiro: 1 mg/kg per day), losartan (SHR-Los: 20 mg/kg per day) or saline. Rats were followed up until week 72 of age and cardiovascular parameters were repeatedly assessed by echocardiography, radiotelemetry of blood pressure and 24-h urine collection. End-point measurements included direct left ventricular contractility and relaxation, as well as cardiac and renal histomorphology.
  
  
  RESULTS
  Transient spironolactone treatment reduced blood pressure up to 36 weeks of age and cardiac and renal collagen deposition and tubular atrophy up to 72 weeks of age compared to untreated SHR. Pulse pressure was higher in SHR-Spiro compared to SHR-Los. Cardiac hypertrophy, albuminuria and glomerulosclerosis were not attenuated in SHR-Spiro compared to untreated SHR up to 72 weeks of age, whereas the effects in SHR-Los were ameliorated.
  
  
  CONCLUSIONS
  Although transient spironolactone treatment leads to prolonged blood pressure reduction and reduced collagen deposition, long-term organ protection only partially exists. Thus, transient spironolactone treatment is less effective than transient losartan treatment.
authors.affiliation: Department of Pharmacology and Toxicology, University Maastricht, The Netherlands. marcus.baumann@lrz.tum.de
authors.forename: Marcus
authors.initials: M
authors.lastname: Baumann
authors.forename: J J Rob
authors.initials: JJ
authors.lastname: Hermans
authors.forename: Ben J A
authors.initials: BJ
authors.lastname: Janssen
authors.forename: Carine
authors.initials: C
authors.lastname: Peutz-Kootstra
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.forename: Uwe
authors.initials: U
authors.lastname: Heemann
authors.forename: Jos F M
authors.initials: JF
authors.lastname: Smits
authors.forename: Harry A J Struijker
authors.initials: HA
authors.lastname: Boudier
mesh_terms: D000367:Age Factors; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019808:Losartan / Q000627:therapeutic use*; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D013148:Spironolactone / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D017931:DNA Primers; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D003094:Collagen; D019808:Losartan