Attenuation of acetylcholine-induced vasoconstriction by L-arginine is related to the progression of atherosclerosis

Otsuji, Satoru; Nakajima, Osamu; Waku, S; Kojima, Shigeyuki; Hosokawa, Hiroshi; Kinoshita, Isao; Ōkubo, Tomoyuki; Tamoto, Shigemi; Takada, Kiyoshi; Ishihara, Tadashi; Osawa, N

doi:10.1016/0002-8703(95)90388-7

Cited by 32 publications

(16 citation statements)

References 34 publications

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“…Regulation of nitric oxide synthases and bioavailability of their product therefore become critical for the development and progression of vascular diseases, such as atherosclerosis. Several lines of evidence indicate that endothelium-dependent vascular relaxation is impaired in cholesterol-fed animals (Kojda et al, 1998) or in isolated human coronary arteries (Forstermann et al, 1988) and the impairment is correlated with the degree of atherosclerosis (Otsuji et al, 1995). Administration of l-arginine (Aji et al, 1997; Boger et al, 1997) or tetrahydrobiopterin (Hattori et al, 2007; Tiefenbacher et al, 2000) attenuates atherosclerotic lesion progression, whereas administration of NOS inhibitors block this protective effect (Wang et al, 1996), signifying a direct link between NO and atherosclerosis lesion formation.…”

Section: Endothelial Nitric Oxide and Atherosclerosismentioning

confidence: 99%

Endothelial nitric oxide (NO) and its pathophysiologic regulation

Chatterjee¹,

Catravas²

2008

Vascular Pharmacology

212

163

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Nitric oxide (NO) is a gaseous lipophilic free radical generated by three distinct isoforms of nitric oxide synthases (NOS), type 1 or neuronal (nNOS), type 2 or inducible (iNOS) and type 3 or endothelial NOS (eNOS). Expression of eNOS is altered in many types of cardiovascular disease, such as atherosclerosis, diabetes and hypertension. The ubiquitous chaperone heat shock protein 90 (hsp90) associates with NOS and is important for its proper folding and function. Current studies point toward a therapeutic potential by modulating hsp90-NOS association in various vascular diseases. Here we review the transcriptional regulation of endothelial NOS and factors affecting eNOS activity and function, as well as the important vascular pathologies associated with altered NOS function, focusing on the regulatory role of hsp90 and other factors in NO-associated pathogenesis of these diseases. Keywords nitric oxide; hsp90; cardiovascular disease Transcriptional and post-transcriptional regulation of eNOS in endothelial cellsEndothelial cells have a constitutive expression of eNOS and like other constitutively expressed proteins, the eNOS promoter lacks the typical TATA box. Instead, it has other multiple cisregulatory DNA sequences like SP-1, GATA, activator protein-1, activator protein-2, nuclear factor-1, sheer stress response elements and sterol-regulatory elements (Marsden et al., 1993). The presence of these consensus sites is consistent with evidence showing that levels of eNOS transcripts are elevated by sheer stress (Davis et al., 2001;Woodman et al., 2005), exercise (Sessa et al., 1994;Yang et al., 2002) and hypoxia (Le Cras et al., 1996). Regulation of eNOS transcription by estrogens is still a matter of debate (Arnal et al., 1996;Kleinert et al., 1998), however, estradiol relaxes rat aortic segments via endothelium-dependent andindependent mechanisms involving the NO-cGMP signaling system (Abou-Mohamed et al., 2003). Both lipopolysaccharide (Arriero et al., 2000) and tumor necrosis factor-α (Yoshizumi et al., 1993) decrease eNOS gene expression by reducing the stability of eNOS mRNAs. Basal human eNOS transcription is controlled by two regulatory regions, the positive regulatory Address correspondence to: Dr. John D. Catravas Vascular Biology Center Medical College of Georgia Augusta, GA 30912-2500 USA e-mail: jcatrava@mcg.edu tel: +1-706-721-6338 fax: +1-706-721-9799. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Searles, 2006). Moreover, these regions also contain differentially methylated nucleotides that restrict eNOS transcription largely in vascular endothel...

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Section: Endothelial Nitric Oxide and Atherosclerosismentioning

confidence: 99%

Endothelial nitric oxide (NO) and its pathophysiologic regulation

Chatterjee¹,

Catravas²

2008

Vascular Pharmacology

212

163

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“…Brachial artery FMD is largely dependent upon endothelial NO elaboration [21]. Impairment of NOmediated vasodilation is a sensitive indicator of the atherosclerotic process, since it occurs early during the development of atherosclerosis [22], and improves early during the regression of atherosclerotic lesions [23,24]. In humans, the degree of endothelial dysfunction is associated with the number of cardiovascular risk factors present in an individual [25].…”

Section: Discussionmentioning

confidence: 99%

Elevation of asymmetrical dimethylarginine may mediate endothelial dysfunction during experimental hyperhomocyst(e)inaemia in humans

et al. 2001

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Hyperhomocyst(e)inaemia is associated with endothelial dysfunction in animals and humans. Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inaemia are poorly understood, but may involve impaired bioavailability of endothelium-derived nitric oxide (NO). We hypothesized that acute elevation of homocyst(e)ine by oral methionine loading may stimulate the formation of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, due to a transmethylation reaction during the formation of homocyst(e)ine from methionine. We studied nine healthy human subjects (five males, four females) aged 29+/-2 years. Flow-mediated vasodilation (FMD) in the brachial artery (endothelium-dependent) and vasodilation induced by nitroglycerine (endothelium-independent) were measured with high-resolution ultrasound before and 8 h after oral methionine (100 mg/kg in cranberry juice) or placebo (cranberry juice), on separate days and in random order. Plasma homocyst(e)ine and ADMA concentrations were measured by specific HPLC methods. After a methionine bolus, elevation of homocyst(e)ine (28.4+/-3.5 micromol/l) was associated with an increased plasma concentration of ADMA (2.03+/-0.18 micromol/l) and reduced FMD (1.54+/-0.92%). Placebo had no effect on these parameters. There was a significant inverse linear relationship between ADMA concentration and FMD (r=-0.49; P<0.05), which was stronger than the relationship between the homocyst(e)ine concentration and FMD (r=-0.36; not significant). We conclude that acute elevation of the homocyst(e)ine concentration impairs vascular endothelial function by a mechanism in which an elevated concentration of ADMA may be involved. This finding may have importance for understanding the mechanism(s) leading to homocyst(e)ine-associated vascular disease, and its potential treatment.

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“…These studies are consistent with observations in the cardiac catheterization laboratory, demonstrating that in patients with stable angina, syndrome X, or with transplant vasculopathy, intravenous infusions of L-arginine can improve coronary blood flow response to acetylcholine (an agonist of NO release). [77,[86][87][88][89]. In young men with documented coronary artery disease, an endothelial vasodilator dysfunction of the brachial artery also exists.…”

Section: Efficacy Of L-arginine In Clinical Trialsmentioning

confidence: 99%