Key result
In hyperlipidemic rabbits, telmisartan increased ACh-induced nitric oxide by 5.5 nmol/l and reduced plaque area more significantly than candesartan or control.
Why the study?
Does telmisartan improve nitric oxide bioavailability and reduce atherosclerotic change in genetically hyperlipidemic rabbits?
Does telmisartan improve nitric oxide bioavailability and reduce atherosclerotic change in genetically hyperlipidemic rabbits?
Telmisartan improves nitric oxide bioavailability and reduces atherosclerotic changes in hyperlipidemic rabbits through PPAR gamma-mediated effects, demonstrating benefits beyond the standard ARB class effect.
Should not change ARB selection in patients; leaves open whether PPARγ effects translate beyond this rabbit model.
OBJECTIVE: Telmisartan is a unique angiotensin II (Ang II) receptor blocker (ARB) with selective peroxisome proliferator-activated receptor-gamma (PPAR gamma). We therefore investigated the effects of telmisartan on endothelial function and atherosclerotic change in genetically hyperlipidemic rabbits, compared with candesartan, an ARB without PPAR gamma activity. METHODS: A total of 30 Watanabe heritable hyperlipidemic (WHHL) rabbits equally derived (n = 6 each) were treated with (1) vehicle (control), (2) GW9662, a PPAR gamma antagonist (0.5 mg/kg per day), (3) telmisartan (5 mg/kg per day), (4) telmisartan + GW9662, (5) candesartan (5 mg/kg per day) for 8 weeks. After treatment, acetylcholine (ACh)-induced nitric oxide production was measured as a surrogate for endothelium protective function, and vascular nitrotyrosine (a product of superoxide and nitric oxide) was measured for assessing dysfunctional endothelial nitric oxide synthase activity. Plaque area was quantified by histology. RESULTS: Telmisartan increased ACh-induced nitric oxide by 5.5 nmol/l, significantly more than control. Interestingly, cotreatment with GW9662 significantly attenuated telmisartan-induced ACh-induced nitric oxide almost to the levels observed with candesartan. Vascular nitrotyrosine concentration was 1.4 pmol/mg protein in the control group and significantly higher than that in the telmisartan or candesartan group. The lowest nitrotyrosine concentration was observed in the telmisartan group, which was significantly lower than that in the candesartan or telmisartan + GW9662 group. Histology of the thoracic aorta revealed that the plaque area was more significantly decreased in the telmisartan group than in the candesartan or telmisartan + GW9662 group. CONCLUSION: In addition to a class effect of ARBs, telmisartan may have additional effects on nitric oxide bioavailability and atherosclerotic change through its PPAR gamma-mediated effects in genetically hyperlipidemic rabbits.
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Ikejima et al. (2008) studied Hyperlipidemia (n=30). Telmisartan vs. Vehicle (control), GW9662, telmisartan + GW9662, and candesartan was evaluated on Acetylcholine (ACh)-induced nitric oxide production and vascular nitrotyrosine concentration. In hyperlipidemic rabbits, telmisartan increased ACh-induced nitric oxide by 5.5 nmol/l and reduced plaque area more significantly than candesartan or control.
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