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Combination therapy with telmisartan and spironolactone alleviates L-NAME exacerbated nephrosclerosis with an
Toshiaki Takahashi1, Hidehiko Ono, Yuko Ono
1Department of Hypertension and Cardiorenal Disease, Dokkyo Medical University, Tochigi, Japan.
International Heart Journal
|November 14, 2007
Summary
Combined therapy with telmisartan and spironolactone effectively reduces hypertensive renal injury in rats by modulating PPAR-gamma and TGF-beta1, independent of blood pressure changes.
Area of Science:
- Nephrology
- Pharmacology
- Hypertension Research
Background:
- Spontaneously hypertensive rats (SHR) treated with L-NAME serve as a model for malignant hypertension, exhibiting renal tissue injury.
- Angiotensin II type 1 and aldosterone receptor blockade are potential therapeutic strategies for hypertensive renal damage.
Purpose of the Study:
- To evaluate the renoprotective effects of blocking angiotensin II type 1 and aldosterone receptors.
- To investigate the impact of these receptor blockades on renal mRNA levels of peroxisome proliferation-activated receptors-gamma (PPAR-gamma) and transforming growth factor-beta (1) (TGF-beta(1)).
Main Methods:
- Five groups of male SHR were treated for 3 weeks: control, L-NAME, L-NAME + spironolactone (SPRL), L-NAME + telmisartan (TELM), and L-NAME + combination therapy (COMB).
- Measurements included urinary protein excretion, glomerular injury score, blood pressure, perivascular cell infiltration, fibrosis, nitric oxide excretion, and interlobular artery wall-to-lumen ratio.
- Renal tissue mRNA levels of PPAR-gamma and TGF-beta(1) were analyzed.
Main Results:
- SPRL, TELM, and COMB groups showed reduced urinary protein and glomerular injury compared to L-NAME alone.
- Only the TELM group exhibited significant blood pressure reduction.
- TELM and COMB groups demonstrated decreased perivascular infiltration and fibrosis, with increased PPAR-gamma and decreased TGF-beta(1) mRNA levels.
- The COMB group uniquely showed recovered nitric oxide excretion and reduced interlobular artery wall-to-lumen ratio.
Conclusions:
- Combined telmisartan and spironolactone therapy alleviates hypertensive renal injury in SHR, irrespective of blood pressure reduction.
- The renoprotective effects are associated with PPAR-gamma activation and TGF-beta(1) inhibition, suggesting anti-inflammatory and antifibrotic mechanisms.
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