TY - JOUR
T1 - Transient prehypertensive treatment in spontaneously hypertensive rats
T2 - A comparison of spironolactone and losartan regarding long-term blood pressure and target organ damage
AU - Baumann, Marcus
AU - Hermans, J. J.Rob
AU - Janssen, Ben J.A.
AU - Peutz-Kootstra, Carine
AU - Witzke, Oliver
AU - Heemann, Uwe
AU - Smits, Jos F.M.
AU - Boudier, Harry A.J.Struijker
PY - 2007/12
Y1 - 2007/12
N2 - 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.
AB - 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.
KW - Blood pressure development
KW - Hypertension
KW - Renin-angiotensin system
KW - Spironolactone
KW - Target organ protection
KW - Transient prehypertensive treatment
UR - http://www.scopus.com/inward/record.url?scp=35848952288&partnerID=8YFLogxK
U2 - 10.1097/HJH.0b013e3282ef84f8
DO - 10.1097/HJH.0b013e3282ef84f8
M3 - Article
C2 - 17984673
AN - SCOPUS:35848952288
SN - 0263-6352
VL - 25
SP - 2504
EP - 2511
JO - Journal of Hypertension
JF - Journal of Hypertension
IS - 12
ER -