Diminished <scp>L</scp>-arginine bioavailability in hypertension

Moss, Monique Bandeira; Brunini, Tatiana M.C.; Moura, Roberto Soares de; Malagris, Lúcia Emmanoel Novaes; Roberts, Norman B.; Ellory, J. C.; Mann, Giovanni E.; Ribeiro, Antonio da Silva

doi:10.1042/cs20030412

Cited by 70 publications

(81 citation statements)

References 38 publications

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“…An association between L-arginine and hypertension has been suggested in 2 smaller previous studies. 39,40 This apparently paradoxical association may be attributable to abnormalities in L-arginine transport via system yϩ, which may limit intracellular availability or L-arginine for NO synthesis. 39,40 This transport system has been shown to be abnormal in hypertension.…”

Section: Large Artery Stiffness Hypertension and Arterial Hemodynamicsmentioning

confidence: 99%

Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics, and Subclinical Vascular Disease

Chirinos¹,

David²,

Bralley³

et al. 2008

Hypertension

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Abstract-Endogenous NO synthase inhibitors (end-NOSIs) have been associated with cardiovascular risk factors and atherosclerosis. In addition, end-NOSIs may directly cause hypertension through hemodynamic effects. We aimed to examine the association between end-NOSI asymmetrical dimethylarginine (ADMA) and N-guanidino-monomethylarginine (NMMA), subclinical atherosclerosis, and arterial hemodynamics. We studied 922 adults participating in a population-based study (PREVENCION Study) and examined the correlation between end-NOSI/L-arginine and arterial hemodynamics, carotid-femoral pulse wave velocity, and carotid intima-media thickness using linear regression. ADMA, NMMA, and L-arginine were found to be differentially associated with various classic cardiovascular risk factors. ADMA and NMMA (but not L-arginine) were significant predictors of carotid intima-media thickness, even after adjustment for cardiovascular risk factors, C-reactive protein, and renal function. In contrast, ADMA and NMMA did not predict carotid-femoral pulse wave velocity, blood pressure, or hemodynamic abnormalities. Higher L-arginine independently predicted systolic hypertension, higher central pulse pressure, incident wave amplitude, central augmented pressure, and lower total arterial compliance but not systemic vascular resistance or cardiac output. We conclude that ADMA and NMMA are differentially associated with cardiovascular risk factors, but both end-NOSIs are independent predictors of carotid atherosclerosis. In contrast, they are not associated with large artery stiffness, hypertension, or hemodynamic abnormalities. Our findings are consistent with a role for asymmetrical arginine methylation in atherosclerosis but not in large artery stiffening, hypertension, or long-term hemodynamic regulation. L-Arginine is independently associated with abnormal pulsatile (but not resistive) arterial hemodynamic indices, which may reflect abnormal L-arginine transport, leading to decreased intracellular bioavailability for NO synthesis. (Hypertension. 2008;52:1051-1059.)

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Section: Large Artery Stiffness Hypertension and Arterial Hemodynamicsmentioning

confidence: 99%

Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics, and Subclinical Vascular Disease

Chirinos¹,

David²,

Bralley³

et al. 2008

Hypertension

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“…This is of particular interest as it remains to be determined why only a subset of subjects with obesity subsequently develop hypertension. 62 In this context, it is of interest that even normal weight subjects with essential hypertension have reduced l-arginine transport and NO bioavailability, 63 indicating that impaired l-arginine-NO pathway is associated with hypertension regardless of the underlying cause. Furthermore, a functionally relevant genetic polymorphism relating to l-arginine transport is present in human essential hypertension.…”

Section: Are No Bioavailability and L-argininementioning

confidence: 99%

“…62 En este contexto, es interesante destacar que incluso sujetos con peso normal e hipertensión esencial presentaron disminución del transporte de L-arginina y de la disponibilidad de NO, 63 lo que indica que la alteración en la vía L-arginina-NO se relaciona con la hipertensión independientemente de la causa subyacente. Además, un polimorfismo gené-tico funcionalmente relevante relacionado con el transporte de L-arginina se encuentra presente en la hipertensión esencial en humanos.…”

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Say NO to Obesity-Related Hypertension

2016

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O besity and its complications represent one of the major emerging challenges for the developed world. 1,2 Hypertension is a common sequelae of obesity, 3,4 and the obesity pandemic is estimated to contribute to 75% of cases of hypertension in men and 65% in women.1 Frequently, subjects with obesity are resistant to standard antihypertensive medication, 4 and poor understanding of the precise mechanisms underlying the link between obesity and hypertension has presented roadblocks for the development of new and effective therapy. 4 In this context, we recently found that obesity is associated with reduced nitric oxide (NO) bioavailability caused by impaired transport of its substrate l-arginine and that augmentation of endothelial l-arginine transport prevents experimental obesity-induced hypertension.5 Findings by others also provide clear evidence that endothelial dysfunction plays an important role in the pathogenesis of hypertension 6,7 including that associated with obesity. 8In the current review, we will discuss the role of the l-arginine-NO pathway in the long-term regulation of blood pressure, its complex inter-relationship with other key neurohormonal and biochemical determinants of arterial pressure, and the way in which this system becomes deranged in obesity-related hypertension. l-Arginine-NO PathwayNO is well recognized as a pivotal endogenous modulator of vascular tone and endothelial function.9 l-Arginine is the sole substrate for NO formation and transport of extracellular l-arginine via cationic amino acid transporter-1 (CAT1) is a rate limiting factor for endothelial NO synthase (eNOS)-dependent NO formation (Figure 1). [9][10][11] This occurs despite the fact that intracellular concentration of l-arginine far exceeds the Michaelis constant K m of eNOS for l-arginine, and this phenomenon is commonly referred to as the l-arginine paradox. 9 The precise factors underlying this paradox remain to be determined, but some of the proposed mechanisms include sequestration of intracellular l-arginine into pools that are not accessible to membrane-bound eNOS, the presence of endogenous eNOS inhibitors such as asymmetrical dimethylarginine and colocalization of CAT1, and eNOS within the plasma membrane of endothelial cells, which facilitates the use of extracellular l-arginine for eNOS-dependent NO formation.9-11 Regardless of the mechanism(s) involved, the presence of the l-arginine paradox creates a crucial role for l-arginine transporters in regulating NO bioavailability and consequently endothelial function. Does Endothelial Dysfunction Precede Hypertension in the Setting of Obesity?Although there is a plethora of data to support an association between endothelial dysfunction and hypertension, [12][13][14] the precise relationship between these 2 phenomena remains complex and undefined. Weisbrod et al 15 recently demonstrated that endothelial function as measured by aortic relaxation to acetylcholine ex vivo was impaired within 2 months of placing mice on a high fat, high sucrose diet. Howeve...

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“…Although the results support our hypothesis, it is necessary to determine whether L-arginine supplementation in chicks indeed increases NO and/or cGMP production in the aortic wall. It has been reported that the uptake of L-arginine into platelets from hypertensive humans and the transport of L-arginine into red blood cells of hypertensive rats are lower than those in normotensive controls (27); L-citrulline production was also reduced in platelets from hypertensive humans (25). In contrast, L-arginine treatment increased the NO content of ischemic myocardium and reduced apoptosis of myocytes (21).…”

Section: Discussionmentioning

confidence: 99%

Do incremental increases in blood pressure elicit neointimal plaques through endothelial injury?

Ruiz-Feria

Yang

Nishimura

2004

American Journal of Physiology-Regulatory, Integrative and Comp

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Fowl (males more than females) show maturation-dependent rises in blood pressure (BP) and formation of neointimal plaques (NPs), resembling balloon catheter injury-induced neointima, in the abdominal aorta (AbA) just above the bifurcation. The plaque comprises neointimal cells containing abundant endoplasmic reticulum and extracellular matrix. Hence, we investigated whether rapid incremental BP increases in male chicks trigger NP formation, possibly via endothelial injury in hemodynamically selective areas. In 6-wk-old chicks (n ϭ 8) treated 4 wk with solvent (Sv; minipump) or arginine supplement (Arg; 0.3% in drinking water), BP increased from 140 Ϯ 5 to 159 Ϯ 4 (Sv) and from 138 Ϯ 4 to 157 Ϯ 3 (Arg) mmHg, whereas propranolol treatment (Prop, 8 mg⅐kg Ϫ1 ⅐day Ϫ1; minipump) prevented the rise. Arg and Prop groups had, respectively, 73% and 77% smaller (P Ͻ 0.05) NP areas and 19% and 25% less (P Ͻ 0.01) AbA medial thickness than Sv controls. In 16-wk-old cockerels, established BP remained high after Sv and Arg treatments. In the Prop group, BP decreased, but neither NP area nor medial thickness was lower than in the Sv group, whereas the Arg group showed greater NP area and medial thickness. Pulse pressure, determined by intravascular transducer, increased as the pulse wave descended the aorta. The results suggest that maturation-dependent rises in BP in chicks may trigger NP formation in the lower segment of the AbA, which was prevented by inhibition of BP increase, or via a possible increase in nitric oxide availability. BP reduction exerts no effect once BP reaches a plateau. Involvement of endothelial injury leading to NP formation and hemodynamic forces selective for the lesion-prone area remain to be determined. arginine supplement; nitric oxide; hypertension; atherosclerosis; fowl model; pulse pressure; endothelial dysfunction; endothelial nitric oxide synthase uncoupling BIRDS, particularly fowl, have higher blood pressure (BP) than most mammals. In both male and female fowl, BP is already ϳ150 mmHg at 2-3 wk after birth, and at plateau levels, mean BP is higher in males (194 Ϯ 4.6 mmHg) than in females (169 Ϯ 3.1 mmHg) (13,29,30). In males, BP tends to increase with maturation and/or age, whereas an age-dependent change is not clear in females (30). Before sexual maturation, vascular neointimal plaques (NPs), comprising deformed endothelial cells, proliferating neointimal cells of synthetic phenotype, increased endoplasmic reticulum, and abundant extracellular matrix, are spontaneously formed without a high-cholesterol or high-fat diet (30). The NP lesions are seen in the abdominal aorta, most frequently just before the aortic bifurcation into the ischiadic arteries (referred to as the lesion-prone area); the size of the NP area increases with maturation and/or age, whereas vascular smooth muscle (SM) exhibits adaptive hypertrophy (30). In humans, aging and hypertension are major factors in the induction of arterial hardening (6, 28), and increased brachial pulse pressure (PP), aortic pulse wave velocity ...

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Diminished L-arginine bioavailability in hypertension

Cited by 70 publications

References 38 publications

Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics, and Subclinical Vascular Disease

Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics, and Subclinical Vascular Disease

Say NO to Obesity-Related Hypertension

Do incremental increases in blood pressure elicit neointimal plaques through endothelial injury?

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