Telmisartan Decreases Plasma Levels of Asymmetrical Dimethyl-L-Arginine and Improves Lipid and Glucose Metabolism and Vascular Function

Abstract

SummaryTelmisartan is an angiotensin II receptor blocker (ARB) and also an activator of peroxisome proliferator-activated receptor-γ (PPAR-γ). We investigated whether telmisartan improves vascular endothelial function in patients with essential hypertension with the production of endothelial nitric oxide synthase (eNOS) through PPAR-γ.Telmisartan was administered to 15 patients with essential hypertension. To assess vascular function, asymmetric dimethylarginine (ADMA), an eNOS inhibitor synthesized by endothelial cells, and the pulse-wave velocity (PWV) were measured. The serum levels of lipid, glucose, and glycohemoglobin (HbA1c) were also evaluated before and after treatment. Telmisartan therapy significantly decreased the blood pressure and total-and LDL-cholesterol levels. HbA1c was also significantly improved but not in fasting plasma glucose. The serum levels of ADMA were significantly decreased (0.48 ± 0.08 to 0.42 ± 0.05 nmol/mL; P = 0.01). PWV values were significantly decreased by telmisartan from 1,822.5 ± 352.3 to 1,661.5 ± 299.8 cm/second (P = 0.04*). Telmisartan decreased PWV presumably via the activation of PPAR-γ , suggesting that this agent improves vascular endothelial function via its pleiotropic effects, a mechanism that is different from its hypotensive effects. (Int Heart J 2009; 50: 73-83) Key words: Telmisartan, Vascular endothelial function, Essential hypertension, PPAR-γ , ADMA THE impairment of endothelium causes atherosclerosis, 1) and consequently cerebrovascular and cardiovascular accidents, and is related to poor clinical outcome. Nitric oxide (NO) is a potent vasodilator produced by nitric oxide synthase (NOS) in endothelium, and controls vascular function via regulation of its metabolism.2,3) As a factor regulating NOS activity in vivo, asymmetric dimethylarginine (ADMA), an endogeneous competitive inhibitor of NOS activFrom the

High-Dose Treatment With Telmisartan Induces Monocytic Peroxisome Proliferator-Activated Receptor-γ Target Genes in Patients With the Metabolic Syndrome

“…24 Furthermore, the results regarding LDL cholesterol levels are somewhat surprising, because previous studies have shown that ARBs either have no effect or decrease LDL cholesterol. 15,28,[35][36][37][38] In fact, all of the studies using telmisartan did show a positive effect. The discrepancy between our results and the published data may relate to the doses used.…”

Effects of Eicosapentaenoic Acid on Asymmetric Dimethylarginine in Patients in the Chronic Phase of Cerebral Infarction: A Preliminary Study

“…15 In addition, it has been indicated that drugs that work on the renin-angiotensin system, such as ARB and angiotensin-converting enzyme, possess the ADMA reduction action, [16][17][18] and that telmisartan having the PPAR-g activation action particularly reduces ADMA. 19,20 Regarding the correlation between EPA and ADMA, Eid et al 21 conducted a study in which n-3 polyunsaturated fatty acid was given to patients with hyperlipidemia. They reported that although no change in ADMA was observed in the group, the decrease in the L-arginine/ADMA ratio because of aging was more suppressed than it was in the placebo group.…”

Therapeutic interventions using a combination of Telmisartan and omega 3-fatty acids in sodium arsenite-induced vascular endothelial dysfunction in rats: modulation through ATP-sensitive K+ channels and eNOS

“…Studies have demonstrated that pharmacological blockade of reninangiotensin system (RAS) by angiotensin-II type 1 receptor blocker (ARB) class of antihypertensive agents such as telmisartan offers favorable cardiovascular effects [17][18][19]. Its partial peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist activity which is achievable at therapeutic doses is responsible for anti-inflammatory, antioxidative and antiproliferative effects on vascular wall, thus reducing the risk for atherosclerosis, in addition to improving glucose and lipid profiles [20].…”