Potential target sites to modulate vascular endothelial dysfunction: Current perspectives and future directions

Balakumar, Pitchai; Kaur, Tajpreet; Singh, Manjeet

doi:10.1016/j.tox.2007.12.011

Cited by 57 publications

(34 citation statements)

References 215 publications

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“…NO is generated in the endothelium during the conversion of L-arginine to L-citrulline in the presence of endothelial nitric oxide synthase (eNOS), which requires Ca 2? calmodulin, flavin adenine nucleotide (FAD), flavin mononucleotide (FMN) and tetrahydrobiopterin (BH4) as cofactors for its activation [18][19][20]. The partial loss of the balance between endothelium-mediated vasodilation and vasoconstriction is described as vascular endothelial dysfunction (VED), which occurs mainly due to reduction in the synthesis and release of NO, inactivation of eNOS, excessive generation of ROS, uncoupling of eNOS and reduction in antioxidant defense mechanism [21][22][23].…”

Section: Arsenic and Endothelial Dysfunctionmentioning

confidence: 99%

Arsenic Exposure and Cardiovascular Disorders: An Overview

2009

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The incidence of arsenic toxicity has been observed in various countries including Taiwan, Bangladesh, India, Argentina, Australia, Chile, China, Hungary, Peru, Thailand, Mexico and United States of America. Arsenic is a ubiquitous element present in drinking water, and its exposure is associated with various cardiovascular disorders. Arsenic exposure plays a key role in the pathogenesis of vascular endothelial dysfunction as it inactivates endothelial nitric oxide synthase, leading to reduction in the generation and bioavailability of nitric oxide. In addition, the chronic arsenic exposure induces high oxidative stress, which may affect the structure and function of cardiovascular system. Further, the arsenic exposure has been noted to induce atherosclerosis by increasing the platelet aggregation and reducing fibrinolysis. Moreover, arsenic exposure may cause arrhythmia by increasing the QT interval and accelerating the cellular calcium overload. The chronic exposure to arsenic upregulates the expression of tumor necrosis factor-alpha, interleukin-1, vascular cell adhesion molecule and vascular endothelial growth factor to induce cardiovascular pathogenesis. The present review critically discussed the detrimental role of arsenic in the cardiovascular system.

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Section: Arsenic and Endothelial Dysfunctionmentioning

confidence: 99%

Arsenic Exposure and Cardiovascular Disorders: An Overview

2009

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“…Thus, an improvement of ED has become a new important target to treat HT. 3) Measurement of vascular endothelium-derived vasoactive substrates such as von Willebrand factor (vWF), 4) endothelin (ET), 5) and NO can be used to evaluate ED. 6) Among others, hepatocyte growth factor (HGF), as an endothelium specific cytokine extensively expressed in the cardiovascular system, can promote endothelial proliferation and inhibit endothelial apoptosis.…”

Section: Vol 51 No 4 Effects Of Arb On Hgf and Endothelial Functionmentioning

confidence: 99%

Fixed-Dose Telmisartan/Hydrochlorothiazide in Comparison With Losartan/Hydrochlorothiazide in Decreasing Serum Hepatocyte Growth Factor and Improving Endothelial Dysfunction in Hypertensive Patients

Wang

Qian

et al. 2010

Int. Heart J.

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SummaryCombined treatment with an angiotensin II receptor blocker and hydrochlorothiazide (HCT) is advocated to control hypertension (HT). Hepatocyte growth factor (HGF) may be a new marker to evaluate endothelial dysfunction (ED), which is a potential target in treating HT. The aim of the present study was to compare the effects of Telmisartan/HCT with Losartan/HCT on serum HGF and ED in hypertensive patients.Hypertensive patients were randomly divided into a Telmisartan/HCT (group T) or Losartan/HCT group (group L) and received one tablet of either drug per day for 8 weeks. Serum HGF, nitric oxide (NO), plasma von Willebrand factor (vWF), and endothelin (ET) were measured before treatment and after 8 weeks of treatment. Twenty healthy subjects were selected as controls (control group).HGF, vWF, ET, and the ET/NO ratio were higher, and NO was lower in hypertensive patients than those in the control group (all P < 0.01). After treatment for 8 weeks, HGF, vWF and ET decreased, and NO increased significantly in both groups (all P < 0.01). The reductions in BP and HGF and increase in NO (∆NO) were not significantly different between the two groups (all P > 0.05), but the reductions in vWF and ET (∆ET) and ∆ET/∆NO ratio were more obvious in group T than in group L (all P < 0.01). There was no significant correlation between the changes in most of the measured parameters and the extent of BP reduction in either group.Both Telmisartan/HCT and Losartan/HCT could decrease serum HGF and improve ED, which was independent of the antihypertensive effects. However, the improvement in ED may be superior with Telmisartan/HCT than Losartan/ HCT when the BP-lowering effects are the same. (Int Heart J 2010; 51: 252-258) Key words: Angiotensin II receptor blocker, Diuretic, Von Willebrand factor, Nitric oxide, Endothelin, Vascular endothelium H ypertension (HT) has become an important threat to human health in recent decades. Data show that the adult prevalence of HT is 18.8%, however, the rates of recognition, treatment, and control of HT were 30.2%, 24.7%, and 6.1%, respectively, in the Chinese population in 2002, all of which are very low levels.1) There were various underlying reasons, among which the nonappropriate selection of antihypertensive drugs was especially important. Numerous studies have indicated that the control rate of blood pressure (BP) was very low when one type of antihypertensive drug was administered alone; nevertheless, an increase in dose would result in significant side effects. Therefore, low-dose combined administration of antihypertensive drugs is advocated, thus enhancing the control rate of BP and decreasing the side effects.2) Among several protocols, combined treatment with an angiotensin II receptor blocker (ARB) and low-dose hydrochlorothiazide (HCT) is commonly used in clinical practice. Vascular endothelium is the largest endocrine and paracrine organ that can secrete many kinds of vasoactive substances to regulate vasodilatation, maintain the balance of the blood clotting and fibrinolysis sys...

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“…Endothelium is a thin monolayer of specialized epithelium comprising of simple squamous cells that covers the inner surface of entire vasculature [1]. Nitric oxide (NO) is a major mediator released from the endothelium, and it regulates wide spectrum of cardiovascular functions such as vasodilation and inhibition of platelet adhesion and aggregation, and prevention of smooth muscle cell proliferation, migration and vascular inflammation [1,2].…”

Section: Introductionmentioning

confidence: 99%

“…Nitric oxide (NO) is a major mediator released from the endothelium, and it regulates wide spectrum of cardiovascular functions such as vasodilation and inhibition of platelet adhesion and aggregation, and prevention of smooth muscle cell proliferation, migration and vascular inflammation [1,2]. NO is generated in the endothelium during the conversion of Larginine to L-citrulline in the presence of endothelial nitric oxide synthase (eNOS) [3].…”

Section: Introductionmentioning

confidence: 99%

The Novel Role of Fenofibrate in Preventing Nicotine- and Sodium Arsenite-Induced Vascular Endothelial Dysfunction in the Rat

2010

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The present study investigated the effect of fenofibrate, an agonist of PPAR-alpha, in nicotine- and sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg/kg/day, i.p., 4 weeks) and sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) were administered to produce VED in rats. The scanning electron microscopy study in thoracic aorta revealed that administration of nicotine or sodium arsenite impaired the integrity of vascular endothelium. Further, administration of nicotine or sodium arsenite significantly decreased serum and aortic concentrations of nitrite/nitrate and subsequently reduced acetylcholine-induced endothelium-dependent relaxation. Moreover, nicotine or sodium arsenite produced oxidative stress by increasing serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide generation. However, treatment with fenofibrate (30 mg/kg/day, p.o.) or atorvastatin (30 mg/kg/day p.o., a standard agent) significantly prevented nicotine- and sodium arsenite-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentrations of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium-dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Conversely, co-administration of L-NAME (25 mg/kg/day, i.p.), an inhibitor of nitric oxide synthase, markedly attenuated these vascular protective effects of fenofibrate. The administration of nicotine or sodium arsenite altered the lipid profile by increasing serum cholesterol and triglycerides and consequently decreasing high-density lipoprotein levels, which were significantly prevented by treatment with fenofibrate or atorvastatin. It may be concluded that fenofibrate improves the integrity and function of vascular endothelium, and the vascular protecting potential of fenofibrate in preventing the development of nicotine- and sodium arsenite-induced VED may be attributed to its additional properties (other than lipid lowering effect) such as activation of eNOS and generation of NO and consequent reduction in oxidative stress.

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Potential target sites to modulate vascular endothelial dysfunction: Current perspectives and future directions

Cited by 57 publications

References 215 publications

Arsenic Exposure and Cardiovascular Disorders: An Overview

Arsenic Exposure and Cardiovascular Disorders: An Overview

Fixed-Dose Telmisartan/Hydrochlorothiazide in Comparison With Losartan/Hydrochlorothiazide in Decreasing Serum Hepatocyte Growth Factor and Improving Endothelial Dysfunction in Hypertensive Patients

The Novel Role of Fenofibrate in Preventing Nicotine- and Sodium Arsenite-Induced Vascular Endothelial Dysfunction in the Rat

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