Telmisartan Shows an Equivalent Effect of Vitamin C in Further Improving Endothelial Dysfunction After Glycemia Normalization in Type 1 Diabetes

Ceriello, Antonio; Piconi, Ludovica; Esposito, Katherine; Giugliano, Dario

doi:10.2337/dc07-0318

Cited by 41 publications

(26 citation statements)

References 40 publications

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“…Our results are in agreement with those of previous studies showing that short-term (4-12 weeks) treatment with telmisartan improved endothelial function in patients with essential hypertension and diabetes. 24,27,28 In addition to the previous shortterm observations, 24,27,28 we clearly showed the markedly beneficial effect on endothelial function after long-term (1-year) treatment with telmisartan. Furthermore, our study showed for the first time that the improvement in FMD correlated with the reduction in blood pressure and the increase in circulating AN after treatment with telmisartan.…”

Section: Discussionsupporting

confidence: 81%

“…It is tempting to speculate that the anti-inflammatory and antiatherosclerotic effects of telmisartan may contribute to the improvement of endothelial function by increased AN and decreased oxidative stress. 28 There are several limitations in this study. First, it is an open-label study that did not use a placebo or specify other antihypertensive drugs for comparison.…”

Section: Discussionmentioning

confidence: 92%

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Improvement of endothelial function in patients with hypertension and type 2 diabetes after treatment with telmisartan

et al. 2010

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Telmisartan, a selective antagonist for angiotensin type1 receptor and a partial agonist for peroxisome proliferator-activated receptor-c, decreases blood pressure and has been shown to improve glucose and lipid metabolism, suggesting potential cardiovascular protective effects. In this study, we investigated whether long-term treatment with telmisartan improved endothelial function in 35 hypertensive patients with type 2 diabetes mellitus (T2DM). Office and home early morning blood pressure levels and flow-mediated vasodilation (FMD) were evaluated before and after 12 months of treatment with telmisartan. Blood samples were also obtained for measurement of several biochemical parameters and of adiponectin (AN) and highly sensitive C-reactive protein (hs-CRP) before and after treatment. After 12 months of treatment, office and morning blood pressure levels had significantly decreased, and levels of plasma glucose, glycosylated hemoglobin, total cholesterol, triglyceride and low-density lipoprotein cholesterol had also significantly decreased. Plasma AN and high-density lipoprotein cholesterol levels increased, but hs-CRP levels decreased. Furthermore, FMD significantly increased; changes in percent FMD showed a significant negative correlation with changes in systolic and diastolic blood pressure and a significant positive correlation with changes in AN. Stepwise multivariate regression analysis revealed that changes in plasma AN and office systolic blood pressure were both independent determinants for endothelial function after telmisartan treatment. In conclusion, this study shows that long-term treatment with telmisartan improves not only blood pressure and glucose and lipid metabolism but also endothelial function in hypertensive patients with T2DM, possibly by increased circulating AN and decreased blood pressure.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 92%

Improvement of endothelial function in patients with hypertension and type 2 diabetes after treatment with telmisartan

et al. 2010

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“…Accumulation of nitrotyrosine has been documented in vascular endothelium (58,63), heart (57,58), retina (27,52), and kidney (25) of STZ-diabetic rodents as well as circulation (11,10,34), cutaneous vasculature (64), myocardium (32), and kidney (66) of human subjects with diabetes mellitus. In peripheral nervous system, increased nitrotyrosine immunoreactivities have been identified in the sciatic nerve, gray matter of spinal cord, DRG, and vasa nervorum of STZ-diabetic rats and mice, Zucker fatty rats, and Zucker diabetic fatty rats as well as leptin-deficient (ob/ob) and high-fat diet-fed mice (13,16,24,26,48,51,52,54,60,69).…”

Section: Discussionmentioning

confidence: 99%

“…Evidence of the important role of nitrosative stress in diabetic neuropathy in humans is emerging. Increased plasma nitrotyrosine levels have been found to correlate with redistribution of sudomotor responses, an early sign of sympathetic nerve dysfunction, as well as with endothelial dysfunction, an important player in PDN (9,37), in type 1 diabetic subjects (11,10,34).…”

Section: Discussionmentioning

confidence: 99%

Role of nitrosative stress in early neuropathy and vascular dysfunction in streptozotocin-diabetic rats

Obrosova

Drel²,

Oltman³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

107

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Obrosova IG, Drel VR, Oltman CL, Mashtalir N, Tibrewala J, Groves JT, Yorek MA. Role of nitrosative stress in early neuropathy and vascular dysfunction in streptozotocin-diabetic rats. Am J Physiol Endocrinol Metab 293: E1645-E1655, 2007. First published October 2, 2007; doi:10.1152/ajpendo.00479.2007.-Evidence for important roles of the highly reactive oxidant peroxynitrite in diabetic complications is emerging. We evaluated the role of peroxynitrite in early peripheral neuropathy and vascular dysfunction in STZ-diabetic rats. In the first dose-finding study, control and STZ-diabetic rats were maintained with or without the potent peroxynitrite decomposition catalyst Fe(III)tetrakis-2-(N-triethylene glycol monomethyl ether) pyridyl porphyrin (FP15) at 3, 5, or 10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 in the drinking water for 4 wk after an initial 2 wk without treatment for assessment of early neuropathy. In the second study with similar experimental design, control and STZ-diabetic rats were maintained with or without FP15, 5 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 , for vascular studies. Rats with 6-wk duration of diabetes developed motor and sensory nerve conduction velocity deficits, mechanical hyperalgesia, and tactile allodynia in the absence of small sensory nerve fiber degeneration. They also had increased nitrotyrosine and poly(ADP-ribose) immunofluorescence in the sciatic nerve and dorsal root ganglia. All these variables were dose-dependently corrected by FP15, with minimal differences between the 5 and 10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 doses. FP15, 5 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 , also corrected endoneurial nutritive blood flow and nitrotyrosine, but not superoxide, fluorescence in aorta and epineurial arterioles. Diabetes-induced decreases in acetylcholine-mediated relaxation by epineurial arterioles and coronary and mesenteric arteries, as well as bradykinin-induced relaxation by coronary and mesenteric arteries, were alleviated by FP15 treatment. The findings reveal the important role of nitrosative stress in early neuropathy and vasculopathy and provide the rationale for further studies of peroxynitrite decomposition catalysts in long-term diabetic models.OXIDATIVE STRESS resulting from increased production of reactive oxygen species (ROS) and downregulation or insufficient upregulation of antioxidant defense is a well-recognized fundamental mechanism in diabetic complications. Superoxide is a primary free radical produced in diabetic and hyperglycemic conditions. Superoxide is rapidly converted to several other ROS, i.e., hydroxyl radicals (Fenton and Haber-Weiss reactions), peroxynitrite (reaction with nitric oxide), and hydrogen peroxide (reaction catalyzed by intrinsic superoxide dismutase) (22). The rate of superoxide reaction with nitric oxide exceeds by at least one order of magnitude the rates of other aforementioned reactions, which makes peroxynitrite the number one oxidant in biological systems (38,57,71). Peroxynitrite causes the following numerous cytotoxic effects (nitrosative stress): 1) protein nitration and nitrosylation, 2) DNA singl...

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“…Although the important role of oxidative stress in type 1 peripheral diabetic neuropathy (PDN) is well established (2)(3)(4), the contribution of the nitrosative component of free radical and oxidant-induced injury, and, in particular, of the highly reactive oxidant peroxynitrite (5), to diabetes-associated neuropathic changes has not been properly explored. Recent clinical studies revealed increased plasma nitrotyrosine levels and their correlation with endothelial dysfunction and redistribution of sudomotor responses, an early sign of sympathetic nerve dysfunction, in type 1 diabetic subjects (6,7). Furthermore, plasma peroxynitrite generation assessed by the pholasin chemiluminescence test correlated with the diabetic neuropathy impairment score of the lower limbs (8).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate on peripheral neuropathy in a mouse model of type 1 diabetes

Drel

Pacher²,

Vareniuk³

et al. 2007

Int J Mol Med

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Whereas the important role of free radicals in diabetes-associated complications is well established, the contributions of the highly reactive oxidant peroxynitrite have not been properly explored. The present study used a pharmacological approach to evaluate the role of peroxynitrite in peripheral diabetic neuropathy. Control and STZ-diabetic mice were maintained with or without treatment with the potent peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate (FeTMPS), at doses of 5 or 10 mg/kg/day in the drinking water for 3 weeks after an initial 3 weeks without treatment. Mice with a 6-week duration of diabetes developed clearly manifest motor (MNCV) and sensory nerve conduction velocity (SNCV) deficits, thermal hypoalgesia (paw withdrawal, tail-flick, and hot plate tests), mechanical hypoalgesia (tail pressure Randall-Sellito test), tactile allodynia (flexible von Frey filament test), and ~44% loss of intraepidermal nerve fibers. They also had increased nitrotyrosine and poly(ADP-ribose) immunofluorescence in sciatic nerve, grey matter of the spinal cord, and dorsal root ganglion neurons. FeTMPS treatment alleviated or essentially corrected (at a dose of 10 mg/kg/day) MNCV and SNCV deficits, and was associated with less severe small sensory nerve fiber dysfunction and degeneration. Nitrotyrosine and poly (ADP-ribose) immunofluorescence in sciatic nerve, spinal cord, and dorsal root ganglion neurons in peroxynitrite decomposition catalyst-treated diabetic mice was markedly reduced. In conclusion, peroxynitrite contributes to large motor, large sensory, and small sensory fiber neuropathy in streptozotocin-diabetic mice. The findings provide rationale for development of potent peroxynitrite decomposition catalysts for the treatment of diabetic neuropathy.

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Telmisartan Shows an Equivalent Effect of Vitamin C in Further Improving Endothelial Dysfunction After Glycemia Normalization in Type 1 Diabetes

Cited by 41 publications

References 40 publications

Improvement of endothelial function in patients with hypertension and type 2 diabetes after treatment with telmisartan

Improvement of endothelial function in patients with hypertension and type 2 diabetes after treatment with telmisartan

Role of nitrosative stress in early neuropathy and vascular dysfunction in streptozotocin-diabetic rats

Evaluation of the peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate on peripheral neuropathy in a mouse model of type 1 diabetes

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