Sulfhydryl angiotensin-converting enzyme inhibition induces sustained reduction of systemic oxidative stress and improves the nitric oxide pathway in patients with essential hypertension

Napoli, Claudio; Sica, Vincenzo; Nigris, Filomena de; Pignalosa, Orlando; Condorelli, M; Ignarro, Louis J.; Liguori, Ilaria

doi:10.1016/j.ahj.2004.03.025

Cited by 158 publications

(123 citation statements)

References 58 publications

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“…23) Several studies have reported that ARB/ACEI administration significantly decreased the serum levels of ADMA. 5,6,24) In agreement with these studies, our study also showed that telmisartan decreased ADMA levels. The mechanism by which telmisartan decreased the ADMA levels is not well understood, but telmisartan-related decreases in blood pressure, plasma glucose, and lipids may be involved in the mechanism.…”

Section: Discussionsupporting

confidence: 81%

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

et al. 2009

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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

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Section: Discussionsupporting

confidence: 81%

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

et al. 2009

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“…Quinapril has a higher binding affinity for tissue ACE than captopril 15,16 and may increase bradykinin and nitric oxide (NO) more potently. 15,36 NO is the main mediator of FMD 33 and a determinant of arterial elastic properties. 37 Thus, the observed effects of quinapril vs captopril and telmisartan are perhaps due to improved NO bioavailability.…”

Section: Endothelial Functionmentioning

confidence: 99%

Acute effects of renin-angiotensin system blockade on arterial function in hypertensive patients

et al. 2007

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“…Pharmacological agents that have been tested for their ability to modify ADMA levels in humans include drugs that interfere with the renin-angiotensin system (RAS) by either blocking the formation [angiotensin-converting enzyme (ACE) inhibitors] or pharmacological action [angiotensin receptor blockers (ARBs)] of angiotensin II (ANG II). Although some investigators found significant reductions of ADMA levels in patients treated with RAS-blocking agents (2,4,9,15,16,27,42), other studies have failed to confirm these findings (10,40). Sound interpretation of the aforementioned clinical trials is complicated due to differences in study design, study cohorts, treatment regimen, and the use of different bioanalytical methods to determine ADMA levels.…”

mentioning

confidence: 91%

Role of asymmetric dimethylarginine for angiotensin II-induced target organ damage in mice

Jacobi¹,

Maas²,

Cordasic³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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RH, Hilgers KF. Role of asymmetric dimethylarginine for angiotensin II-induced target organ damage in mice. Am J Physiol Heart Circ Physiol 294: H1058-H1066, 2008. First published December 21, 2007 doi:10.1152/ajpheart.01103.2007.-The aim of the present study was to investigate the role of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and its degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH) in angiotensin II (ANG II)-induced hypertension and target organ damage in mice. Mice transgenic for the human DDAH1 gene (TG) and wild-type (WT) mice (each, n ϭ 28) were treated with 1.0 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ANG II, 3.0 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ANG II, or phosphate-buffered saline over 4 wk via osmotic minipumps. Blood pressure, as measured by tail cuff, was elevated to the same degree in TG and WT mice. Plasma levels of ADMA were lower in TG than WT mice and were not affected after 4 wk by either dose of ANG II in both TG and WT animals. Oxidative stress within the wall of the aorta, measured by fluorescence microscopy using the dye dihydroethidium, was significantly reduced in TG mice. ANG II-induced glomerulosclerosis was similar between WT and TG mice, whereas renal interstitial fibrosis was significantly reduced in TG compared with WT animals. Renal mRNA expression of protein arginine methyltransferase (PRMT)1 and DDAH2 increased during the infusion of ANG II, whereas PRMT3 and endogenous mouse DDAH1 expression remained unaltered. Chronic infusion of ANG II in mice has no effect on the plasma levels of ADMA after 4 wk. However, an overexpression of DDAH1 alleviates ANG II-induced renal interstitial fibrosis and vascular oxidative stress, suggesting a blood pressure-independent effect of ADMA on ANG II-induced target organ damage. dimethylarginine dimethylaminohydrolase; hypertension; transgenic ASYMMETRIC DIMETHYLARGININE (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is increasingly recognized as a potential risk factor and prognostic biomarker in cardiovascular disease (38). Thus far, elevated ADMA levels have been associated with all established cardiovascular risk factors (38). Furthermore, recent data from genetic mouse models indicate a causal role for ADMA in the pathophysiology of vascular disease (7,19). ADMA derives from the posttranslational methylation of L-arginine residues within proteins catalyzed by enzymes called protein arginine methyltransferases (PRMTs). Upon proteolysis, methylarginines are released into the circulation. Although ϳ15% of ADMA are excreted via the urine, the major elimination occurs through enzymatic degradation (ϳ85%) (1). The enzyme dimethylarginine dimethylaminohydrolase (DDAH), of which two isoforms with distinct tissue distribution have been described, catalyzes the hydrolysis of ADMA to L-citrulline and dimethylamine (38).Thus far, clinical studies have mostly addressed the prognostic value of ADMA in cardiovascular or kidney disease as well as the impact of pharmacological interventions aimed at lowering ADMA levels ...

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Sulfhydryl angiotensin-converting enzyme inhibition induces sustained reduction of systemic oxidative stress and improves the nitric oxide pathway in patients with essential hypertension

Cited by 158 publications

References 58 publications

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

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

Acute effects of renin-angiotensin system blockade on arterial function in hypertensive patients

Role of asymmetric dimethylarginine for angiotensin II-induced target organ damage in mice

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