Combination Therapy With Telmisartan and Spironolactone Alleviates L-NAME Exacerbated Nephrosclerosis With an Increase in PPAR-.GAMMA. and Decrease in TGF-.BETA.1

Abstract

SUMMARYTo investigate whether the receptor blockades of angiotensin II type 1 and aldosterone receptors can prevent renal tissue injury in relation to the renal tissue mRNA levels of peroxisome proliferation-activated receptors-γ (PPAR-γ) and transforming growth factor-β 1 (TGF-β 1 ) in spontaneously hypertensive rats (SHR) given N G -nitro-L-arginine methyl ester (L-NAME), which is considered a model of malignant hypertension.This study was performed in 5 groups of 17-week-old male SHR treated for 3 weeks as follows: group 1, control; group 2, L-NAME (50 mg/L in drinking); group 3, L-NAME plus aldosterone antagonist, spironolactone (SPRL, 100 mg/kg/day); group 4, L-NAME plus angiotensin II type 1 receptor blocker, telmisartan (TELM, 3 mg/kg/day); group 5, L-NAME plus combination therapy (COMB) with low-dose TELM (1 mg/kg/day) and SPRL (100 mg/kg/day).Urinary protein excretion and the glomerular injury score were significantly reduced in the SPRL, TELM, and COMB groups as compared with the L-NAME group, while significant blood pressure reduction was observed only in the TELM group. In the TELM and COMB groups, the perivascular cell infiltration and fibrosis area were significantly reduced together with the PPAR-γ mRNA increase and TGF-β 1 mRNA decrease. The urinary excretion of nitric oxides was significantly recovered and the wall to lumen ratio of the interlobular artery was significantly reduced only in the COMB group compared with the L-NAME group.Combined administration of 1 mg/kg/day telmisartan and 100 mg/kg/day spironolactone is thought to be effective in alleviating hypertensive renal injuries independently of blood pressure changes. The anti-inflammatory and antifibrotic effects due to PPAR-γ activation and TGF-β 1 inhibition may participate in the renoprotection of this combination therapy. (Int Heart J 2007; 48: 637-647)

Functions of Chitosan-Ferulic Acid Salt for Prevention of Hypertension

“…In the present study, L-NAME was given to SHR as drinking water to generate malignant hypertension (Takahashi, et al, 2007). Development of a preparation that does µmol) after 2 h. In all cases, the upper 80% of BA dissolved in the solution was taken up; the uptake amount increased according to the increment of BA concentration (data not shown).…”

Effect of Angiotensin II Receptor Blocker on Experimental Periodontitis in a Mouse Model of Marfan Syndrome

“…Clinical (12,17) and animal (19,42) studies indicated that the ARBs telmisartan and losartan protected against the progression of aortic aneurysms. Telmisartan was reported to decrease TGF-␤ mRNA levels (43). In addition, ARBs can attenuate canonical SMAD and noncanonical extracellular signal-regulated kinase (ERK) with respect to TGF-␤ signaling (42).…”

Amelioration of chronic cyclosporine A-induced nephrotoxicity by telmisartan in rats

“…Group 1 received normal saline s.c daily, group 2 received Cremophor EL and ethanol (CsA vehicle) s.c daily, group 3 received CsA 25 mg/kg/day s.c once daily (Lee et al, 1999;del Moral et al, 1997) and group 4 received telmisartan 3 mg/kg/day orally in addition to CsA (Takahashi et al, 2007).…”

“…Signalling through the AT 1 receptor results in vasoconstriction and sodium reabsorption, and also promotes cellular growth, hypertrophy, activation of fibroblasts, and extracellular matrix deposition in the kidney (Sugiyama et al, 2005). Telmisartan exerts a variety of pleiotropic effects, including antioxidative, antiapoptotic, and anti-inflammatory effects (Sugiyama et al, 2005;Duan et al, 2009;Takahashi et al, 2007). It acts as a partial agonist of PPAR- (Benson et al, 2004).…”

“…ROS are involved in many of the AngII signalling pathways (Griendling and Ushio-Fukai, 2000). Telmisartan had protective effect in many animals model of renal injury (Sugiyama et al, 2005;Duan et al, 2009;Takahashi et al, 2007). Therefore, it may be a convenient renal-protective drug.…”