In Vivo and In Vitro Evidence for Impaired Arginine Transport in Human Heart Failure

Kaye, David M.; Ahlers, Belinda A.; Autelitano, Dominic J.; Chin-Dusting, Jaye

doi:10.1161/01.cir.102.22.2707

Cited by 64 publications

(65 citation statements)

References 53 publications

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“…In a similar manner, we have shown previously that CAT1 mRNA is significantly decreased in association with decreased arginine uptake in heart failure patients. 29 The rapid actions of CSE suggest a posttranslational modification of CAT1, possibly involving 1 or more cysteine residues given the ability of N-acetyl cysteine to attenuate the effects of CSE and DTNB, a dithiol oxidizing agent, to mimic the actions of CSE. To our knowledge, however, this potential posttranslational mechanism for the regulation of CAT1 has not been reported previously.…”

Section: Discussionmentioning

confidence: 99%

Adverse Effects of Cigarette Smoke on NO Bioavailability

et al. 2006

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Abstract-Endothelial dysfunction is a hallmark of cardiovascular disease, and the L-arginine:NO pathway plays a critical role in determining endothelial function. Recent studies suggest that smoking, a well-recognized risk factor for vascular disease, may interfere with L-arginine and NO metabolism; however, this remains poorly characterized. Accordingly, we performed a series of complementary in vivo and in vitro studies to elucidate the mechanism by which cigarette smoke adversely affects endothelial function. In current smokers, plasma levels of asymmetrical dimethyl-arginine (ADMA) were 80% higher (Pϭ0.01) than nonsmokers, whereas citrulline (17%; PϽ0.05) and N-hydroxy-L-arginine (34%; PϽ0.05) were significantly lower. Exposure to 10% cigarette smoke extract (CSE) significantly affected endothelial arginine metabolism with reductions in the intracellular content of citrulline (81%), N-hydroxy-L-arginine (57%), and arginine (23%), while increasing ADMA (129%). CSE significantly inhibited (38%) arginine uptake in conjunction with a 34% reduction in expression of the arginine transporter, CAT1. In conjunction with these studies, CSE significantly reduced the activity of eNOS and NO production by endothelial cells, while stimulating the production of reactive oxygen species. In conclusion, cigarette smoke adversely affects the endothelial L-arginine NO synthase pathway, resulting in reducing NO production and elevated oxidative stress. In conjunction, exposure to cigarette smoke increases ADMA concentration, the latter being a risk factor for cardiovascular disease. Key Words: smoking Ⅲ endothelium Ⅲ metabolism A therosclerotic coronary and cerebrovascular disease are leading causes of death and disability in the Western world, and cigarette smoking has been clearly identified as a risk factor for coronary artery disease (reviewed by Ambrose and Barua 1 ). In this context, measures of endothelial function have been associated with cardiovascular outcome, 2 and smoking has been widely associated with reduced endothelial function. 3 The endothelium plays a central role in the modulation of vascular tone, the inhibition of platelet aggregation and vascular smooth muscle proliferation, and a key participation in angiogenesis under appropriate conditions. NO is well recognized as playing a pivotal part in these endothelial properties, being produced by the endothelial isoform of NO from its preferred substrate L-arginine. In this context, provision of sufficient L-arginine is critical for the sustained production of NO supply, 4 mediated in endothelial cells (ECs) principally by the type 1 cationic amino acid transporter (CAT1). Previous studies indicate that deleterious actions of cigarette smoke on endothelial function could be mitigated by supplemental L-arginine; 5 however, to date, the precise basis for this interaction remains unclear. One explanation is that cigarette smoke exerts an inhibitory effect on components of the L-arginine:NO pathway to influence NO production. In addition, potential effects of cigar...

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Section: Discussionmentioning

confidence: 99%

Adverse Effects of Cigarette Smoke on NO Bioavailability

et al. 2006

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“…7 In brief, peripheral blood mononuclear cells were incubated in a balanced salt solution with L-arginine in concentrations ranging from 1 to 300 mol/L, incorporating 100 nmol/L [ 3 H]-L-arginine for a period of 5 minutes at 37°C. Uptake was terminated by 3 successive cell pellet washes in ice-cold KrebsHenseleit buffer.…”

Section: Study Protocol For Investigation Of L-arginine Uptake In Permentioning

confidence: 99%

l -Arginine Transport in Humans With Cortisol-Induced Hypertension

et al. 2003

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Abstract-A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d).Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-Arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 mol/L), incorporating 100 nmol/L [ 3 H]-L-arginine for a period of 5 minutes at 37°C. Forearm Key Words: cortisol Ⅲ hypertension, mineralocorticoid Ⅲ nitric oxide Ⅲ arginine Ⅲ human C ortisol, the major naturally occurring human glucocorticoid, is implicated in the pathogenesis of some forms of essential hypertension, 1 but the mechanisms by which cortisol raises blood pressure are not fully defined. Cardiac output is increased but is not essential for the increase, 2 and sympathetic activity is, if anything, decreased. 3 A role for the nitric oxide system in cortisol-induced hypertension has been implicated in animal models of cortisol-induced hypertension; L-arginine, the substrate precursor to nitric oxide, prevents and reverses the development of adrenocorticotropin-induced hypertension in rats. 4 In humans, cortisol-increases in blood pressure occur in association with reductions in plasma nitrate/nitrite concentrations, but no change in plasma arginine or symmetric or asymmetric dimethyl arginine has been observed, indicating that the reductions in nitrate could not be explained by changes in substrate availability or endogenous nitric oxide synthase inhibitors. 5 More recently, using bilateral forearm plethysmography, we have found impaired cholinergic vasodilatation after cortisol administration. Cortisol did not affect the response to sodium nitroprusside, and although N G -monomethyl-L-arginine inhibited cholinergic vasodilation in placebo-treated subjects, it had no additional effect in the presence of cortisol. 6 Taken together, these results are consistent with a role for abnormalities of the nitric oxide system in cortisol-induced hypertension in humans.In the current study, we explored whether cortisol reduces the cellular uptake of L-arginine and whether this mechanism might provide an explanation for the decreased synthesis or secretion of nitric oxide. The study was performed in healthy adult men against a background of a restricted-nitrate diet. L-Arginine transport was assessed in peripheral blood mononuclear cells isolated from these subjects as well as in vivo in the forearm vascular bed. Methods SubjectsHealthy (or disease-free) men were recruited by advertisement. All underwent a physical medical examination and had their medical history recorded. Persons with a history of major illness, including diabetes, cardiovascular disease, respiratory illness, and any contraindication to corticosteroid therapy...

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“…41 An FMD measurement for the purpose of perioperative risk stratification was assessed in a study of 187 patients undergoing high-risk (vascular) surgery. Low flow-mediated dilation was an independent predictor of a cardiac event at 30 days (odds ratio 9) 41 and of late events at 1.2-year follow-up.…”

Section: 80mentioning

confidence: 99%

Coronary Artery Physiology and Intracoronary Ultrasonography

2020

Mayo Clinic Cardiology

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In Vivo and In Vitro Evidence for Impaired Arginine Transport in Human Heart Failure

Cited by 64 publications

References 53 publications

Adverse Effects of Cigarette Smoke on NO Bioavailability

Adverse Effects of Cigarette Smoke on NO Bioavailability

l -Arginine Transport in Humans With Cortisol-Induced Hypertension

Coronary Artery Physiology and Intracoronary Ultrasonography

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