Elevation of an endogenous inhibitor of nitric oxide synthesis in experimental congestive heart failure

Feng, Qingping; Lu, Xiangru; Fortin, Amanda J; Pettersson, Anders; Hedner, Thomas; Kline, Robert L.; Arnold, J. Malcolm O.

doi:10.1016/s0008-6363(97)00242-3

Cited by 92 publications

(58 citation statements)

References 40 publications

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“…11 This level of ADMA alone is probably not sufficient to inhibit NOS activity. However, because methylarginines are concentrated within the cell, 28 a moderate increase in plasma ADMA concentration, as observed in the present study, may reflect a higher increase of the compound in the vicinity of the NOS and thus result in a decrease in plasma NO x concentration. The significant inverse correlation of the percent change in plasma ADMA with the percent change in plasma NO x concentration after both salt loading and restriction may be consistent with this assumption.…”

Section: Mechanism For No Synthesis Suppression By Salt Loadingsupporting

confidence: 54%

“…The significant inverse correlation of the percent change in plasma ADMA with the percent change in plasma NO x concentration after both salt loading and restriction may be consistent with this assumption. Although the origin of elevated plasma ADMA is unknown, the concentration of ADMA was shown to be increased substantially in the plasma of patients with uremia, 11 hypertension, 29 heart failure, 30 and severe atherosclerosis 31 ; in hypercholesterolemic rabbits 32 ; in rats with heart failure 28 ; and in the urine of salt-loaded Dahl salt-sensitive rats. 15 An increased production by methylation of L-arginine 33 and degradation of methylated tissue protein 34 and/or decreased metabolism to citrulline by dimethylarginine dimethylaminohydrolase 33 and excretion from the kidney is likely to contribute to the elevation of plasma ADMA, but this issue still remains to be elucidated.…”

Section: Mechanism For No Synthesis Suppression By Salt Loadingmentioning

confidence: 99%

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Study on the Relationship Between Plasma Nitrite and Nitrate Level and Salt Sensitivity in Human Hypertension

et al. 2000

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Background-High salt intake suppresses the effect of nitric oxide (NO) in the peripheral resistance vessels in animal models. We tested the hypothesis that the modulation of endogenous NO is related to salt sensitivity in human hypertension. Methods and Results-Inpatients with essential hypertension (nϭ24) were maintained on a normal-salt diet (12 g/d NaCl)for 3 days, a low-salt diet (2 g), a high-salt diet (20 to 23 g), and a low-salt diet for 7 days. Normotensive subjects (nϭ16) were maintained on the first 2 salt diets. The hypertensive patients whose average 24-hour blood pressure was increased by Ͼ5% by salt loading were assigned to group 1 (nϭ8) and the others to group 2 (nϭ16). Nitrate plus nitrite (NO x ) was measured by the Griess method, and asymmetrical dimethylarginine (ADMA) by high-performance liquid chromatography. The plasma NO x level during the normal-salt diet was lower in group 1 than in group 2 and the normotensive group. After salt loading, the plasma NO x level was decreased and reversed after the second salt restriction. Plasma ADMA level was increased after salt loading and decreased after salt restriction. The change in plasma NO x level was correlated inversely with those in blood pressure (rϭϪ0.59, Pϭ0.0007) and plasma ADMA level (rϭϪ0.64, Pϭ0.003) after salt loading and restriction. Conclusions-Modulation of NO synthesis by salt intake may be involved in a mechanism for salt sensitivity in human hypertension, presumably via the change in ADMA. (Circulation. 2000;101:856-861.)

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Section: Mechanism For No Synthesis Suppression By Salt Loadingsupporting

confidence: 54%

Section: Mechanism For No Synthesis Suppression By Salt Loadingmentioning

confidence: 99%

Study on the Relationship Between Plasma Nitrite and Nitrate Level and Salt Sensitivity in Human Hypertension

et al. 2000

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“…However, it appears unlikely that either compound would exert a significant effect on either L-arginine transport or endothelial function in the range of reported concentrations. 25,27 Furthermore, in the present study, the abnormality of L-arginine transport was detected in both the forearm circulation and isolated PBMCs, making it unlikely that accumulation of potential transport inhibitors provides a major mechanism for this apparent defect. Alternatively, our in vivo findings could possibly be explained by the presence of antifailure medications, although such therapy has generally been shown to improve endothelial function.…”

Section: Discussionmentioning

confidence: 48%

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

et al. 2000

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Background-The clinical features of congestive heart failure (CHF) result from a complex interaction between reduced ventricular function, neurohormonal activation, and impaired endothelial function. Although endothelial dysfunction has been well documented, the mechanisms that contribute to this abnormality remain unknown. Recent studies, however, indicate a potential therapeutic role for supplemental L-arginine, suggesting the presence of an underlying disorder of L-arginine metabolism. Methods and Results-We used 2 complementary approaches to assess L-arginine transport in control subjects and patients with CHF. During a steady-state intra-arterial infusion of [ 3 H]L-arginine (100 nCi/min), forearm clearance of [ 3 H]L-arginine was significantly reduced in CHF patients compared with forearm kinetics in control subjects (64Ϯ2 versus 133Ϯ14 mL/min, Pϭ0.002). In conjunction with this, [ 3 H]L-arginine uptake by peripheral blood mononuclear cells (PBMCs) was also substantially reduced in heart failure patients compared with controls (V max 10.1Ϯ1.3 versus 49.8Ϯ7.1 pmol/10 5 cells per 5 minutes, PϽ0.001). In association with this finding, we observed a 76% (PϽ0.01) reduction in mRNA expression for the cationic amino acid transporter CAT-1, as assessed by ribonuclease protection assay. Conclusions-These data document both in vivo and in vitro evidence for a marked depression of L-arginine transport in human CHF and therefore provide an explanation for the restorative actions of supplemental L-arginine on vascular function in

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“…This reduced vasodilator influence of NO was present both at rest and during exercise. Although eNOS expression was not altered in the remote myocardium after MI compared with normal myocardium, it is still possible that eNOS activity may have been lower due to loss of eNOS phosphorylation (38) or increased plasma levels of the endogenous eNOS inhibitor asymmetric dimethylarginine (20,23). The reduced NO-mediated vasodilation may have also been due to increased NO scavenging by reactive oxygen species.…”

Section: Integrated Endothelial Control Of Coronary Resistance Vesselmentioning

confidence: 92%

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

Beer

Taverne

Kuster

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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de Beer VJ, Taverne YJ, Kuster DW, Najafi A, Duncker DJ, Merkus D. Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction. Am J Physiol Heart Circ Physiol 301: H1080 -H1089, 2011. First published June 17, 2011 doi:10.1152/ajpheart.01307.2010 is associated with endothelial dysfunction resulting in an imbalance in endothelium-derived vasodilators and vasoconstrictors. We have previously shown that despite increased endothelin (ET) plasma levels, the coronary vasoconstrictor effect of endogenous ET is abolished after MI. In normal swine, nitric oxide (NO) and prostanoids modulate the vasoconstrictor effect of ET. In light of the interaction among NO, prostanoids, and ET combined with endothelial dysfunction present after MI, we investigated this interaction in control of coronary vasomotor tone in the remote noninfarcted myocardium after MI. Studies were performed in chronically instrumented swine (18 normal swine; 13 swine with MI) at rest and during treadmill exercise. Furthermore, endothelial nitric oxide synthase (eNOS) and cyclooxygenase protein levels were measured in the anterior (noninfarcted) wall of six normal and six swine with MI. eNOS inhibition with N -nitro-L-arginine (L-NNA) and cyclooxygenase inhibition with indomethacin each resulted in coronary vasoconstriction at rest and during exercise, as evidenced by a decrease in coronary venous oxygen levels. The effect of L-NNA was slightly decreased in swine with MI, although eNOS expression was not altered. Conversely, in accordance with the unaltered expression of cyclooxygenase-1 after MI, the effect of indomethacin was similar in normal and MI swine. L-NNA enhanced the vasodilator effect of the ETA/B receptor blocker tezosentan but exclusively during exercise in both normal and MI swine. Interestingly, this effect of L-NNA was blunted in MI compared with normal swine. In contrast, whereas indomethacin increased the vasodilator effect of tezosentan only during exercise in normal swine, indomethacin unmasked a coronary vasodilator effect of tezosentan in MI swine both at rest and during exercise. In conclusion, the present study shows that endothelial control of the coronary vasculature is altered in post-MI remodeled myocardium. Thus the overall vasodilator influences of NO as well as its inhibition of the vasoconstrictor influence of ET on the coronary resistance vessels were reduced after MI. In contrast, while the overall prostanoid vasodilator influence was maintained, its inhibition of ET vasoconstrictor influences was enhanced in post-MI remote myocardium. endothelin; nitric oxide; prostacyclin CONGESTIVE HEART FAILURE IS the only major cardiovascular disorder of which the incidence has increased over the past decade, which is principally due to a reduction in mortality associated with acute myocardial infarction (MI). Consequently, MI has become an increasingly important risk factor for the development of congestive heart failure (5). The loss of viable myocardial tissue and the consequent left ve...

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Elevation of an endogenous inhibitor of nitric oxide synthesis in experimental congestive heart failure

Abstract: An endogenous NO synthesis inhibitor ADMA is increased in the circulation of rats with CHF. The increased plasma levels of ADMA may contribute to the decreased endothelium-dependent relaxation in CHF, which is restored by L-arginine, possibly by competitive antagonism of ADMA.

Cited by 92 publications

References 40 publications

Study on the Relationship Between Plasma Nitrite and Nitrate Level and Salt Sensitivity in Human Hypertension

Study on the Relationship Between Plasma Nitrite and Nitrate Level and Salt Sensitivity in Human Hypertension

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

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

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