Augmentation of endothelial function following exercise training is associated with increased <scp>L</scp>-arginine transport in human heart failure

Parnell, Melinda M.; Holst, Diane P.; Kaye, David M.

doi:10.1042/cs20050171

Cited by 30 publications

(22 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At present, there are no pharmacological or genetic-based approaches to augment endothelial l-arginine transport in subjects. We have previously demonstrated that exercise can improve l-arginine transport and endothelial function in subjects with heart failure 71 ; however, it remains to be determined whether this holds true in hypertensive subjects as well. Our data indicate that transfection of adenoviral vector encoding CAT1 into neonatal rat ventricular cardiomyocytes improve NO bioavailability in these cells.…”

Section: Approaches That Can Augment L-arginine Transportmentioning

confidence: 99%

“…En la actualidad, no existen enfoques farmacológicos o genéticos para aumentar el transporte de L-arginina endotelial en sujetos. Previamente hemos demostrado que la actividad física puede mejorar el transporte de L-arginina y la función endotelial en sujetos con insuficiencia cardíaca 71 ; no obstante, aún debe determinarse si esto también en válido en sujetos hipertensos. Nuestros datos indican que la transfección mediante vectores adenovirales que codifican CAT1 en los cardiomiocitos ventriculares de rata neonatal mejora la biodisponibilidad de NO en estas células.…”

Section: Enfoques Que Pueden Aumentar El Transporte De L-argininaunclassified

See 1 more Smart Citation

Say NO to Obesity-Related Hypertension

2016

View full text Add to dashboard Cite

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...

show abstract

Section: Approaches That Can Augment L-arginine Transportmentioning

confidence: 99%

Section: Enfoques Que Pueden Aumentar El Transporte De L-argininaunclassified

Say NO to Obesity-Related Hypertension

2016

View full text Add to dashboard Cite

show abstract

“…Elevated shear stress has been shown to augment L-arginine uptake in cultured endothelial cells in a dose-dependent manner (38), while exercise training has been shown to augment L-arginine uptake in the forearm vasculature of heart failure patients (36). Additionally, exercise training is well known for its ability to improve NO synthesis though activation and increased protein expression of endothelial nitric oxide synthase (eNOS), resulting in improved endothelial function (4,23,50,53).…”

mentioning

confidence: 99%

Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease

Martens

Kuczmarski

Kim

et al. 2014

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

. Voluntary wheel running augments aortic L-arginine transport and endothelial function in rats with chronic kidney disease. Am J Physiol Renal Physiol 307: F418 -F426, 2014. First published June 25, 2014 doi:10.1152/ajprenal.00014.2014.-Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor L-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endotheliumdependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent 5 ⁄6 ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUNϩARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10 Ϫ9 -10 Ϫ5 M) as indicated by a reduced area under the curve (AUC; 44.56 Ϯ 9.01 vs 100 Ϯ 4.58, P Ͻ 0.05) and reduced maximal response (Emax; 59.9 Ϯ 9.67 vs. 94.31 Ϯ 1.27%, P Ͻ 0.05). AUC was not improved by ARG treatment but was significantly improved above SED animals in both RUN and RUNϩARG-treated animals. Maximal relaxation was elevated above SED in RUNϩARG animals only. L-[ 3 H]arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUNϩARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with L-arginine. endothelial dysfunction; chronic kidney disease; L-arginine; exercise ENDOTHELIAL DYSFUNCTION CONTRIBUTES to the development of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) and is primarily associated with a decrease in nitric oxide (NO) production and impaired endothelium-dependent relaxation (EDR) (32). The decline in endothelial function precedes the development of atherosclerosis (17, 48) and has been extensively studied as a potential therapeutic target to treat CVD; however, the specific mechanisms of endothelial dysfunction in CKD have not been fully elucidated. Patients with CKD are more likely to die of CVD than progress to end-stage renal disease (26, 42); therefore, novel treatments to improve endothelial function in CKD are needed to reduce CVD-related mortality in CKD.Insufficient availability of the NO precursor L-arginine likely contributes to reduced NO synthesis in CKD (6). Interestingly, the use of L-arginine in studies of endothelial dysfunction in late-stage CKD has produced mixed results (7, 16) unlike other conditions where it has been largely effective (8,13,15,24). Evidence from cell culture studies suggests that urea and other uremic toxins inhibit L-arginine uptake into endothelial cells (52, 54) by...

show abstract

“…The impairment in endothelialdependent vasodilation is correlated with the degree of exercise intolerance and severity of New York Heart Association class. Exercise training has been shown to improve endothelial NO formation and endothelial-dependent vasodilation in the forearm [58].…”

Section: Exercise In Elderly People With Hfmentioning

confidence: 99%

Exercise and heart failure in the elderly

Kappagoda

Amsterdam

2012

Heart Fail Rev

View full text Add to dashboard Cite

In this review, we will examine the physiological responses to exercise in elderly populations (age > 65 years) with and without evidence of heart failure. Aging per se in both men and women is associated with a ~40% lower maximum oxygen consumption in sedentary subjects. In trained individuals, this value is 25-32% lower. A smaller SV accounts for nearly 50% of these age-related differences, and the remainder is explained by a lower maximal HR and reduced oxygen extraction. Exercise training is also associated with an increase in the arteriovenous O(2) difference in previously sedentary elderly men and women, which probably contributes to the overall beneficial effect of training in the elderly. However, during vigorous exercise (125 W), the cardiac output in the elderly is dependent upon an age-related increase in end-diastolic volume and stroke volume, which "compensates" partially for the age-related decrease in heart rate. Hence, in elderly individuals, the stroke volume during exercise depends upon diastolic filling. The changes that occur in the heart are also associated with an overall reduction in efferent sympathetic nerve activity. Despite this decline, the metaboreflex initiated by receptors in exercising muscles remains the main determinant of sympathetic activation (to maintain blood pressure) during exercise in the elderly. It is recognized that aging is associated with the development of heart failure, particularly in women in whom its prevalence increases >twofold from age 65-69 (6.6%) to age 85 years (14%). Almost half the people presenting with heart failure appear to have normal left ventricular systolic function, a phenomenon that is more common in women. Exercise training in elderly people with and without heart failure appears to have a beneficial effect in terms of enhancing the quality of life and functional capacity. Mortality benefit in the latter has not been established with certainty.

show abstract

Augmentation of endothelial function following exercise training is associated with increased L-arginine transport in human heart failure

Cited by 30 publications

References 40 publications

Say NO to Obesity-Related Hypertension

Say NO to Obesity-Related Hypertension

Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease

Exercise and heart failure in the elderly

Contact Info

Product

Resources

About