Haemodialysis acutely reduces the plasma levels of ADMA without reversing impaired NO-dependent vasodilation

Abstract

End-stage renal disease patients have endothelial dysfunction and high plasma levels of ADMA (asymmetric omega-NG,NG-dimethylarginine), an endogenous inhibitor of NOS (NO synthase). The actual link between these abnormalities is controversial. Therefore, in the present study, we investigated whether HD (haemodialysis) has an acute impact on NO-dependent vasodilation and plasma ADMA in these patients. A total of 24 patients undergoing maintenance HD (HD group) and 24 age- and gender-matched healthy controls (Control group) were enrolled. The increase in forearm SkBF (skin blood flow) caused by local heating to 41 degrees C (SkBF41), known to depend on endothelial NO production, was determined with laser Doppler imaging. SkBF41 was expressed as a percentage of the vasodilatory reserve obtained from the maximal SkBF induced by local heating to 43 degrees C (independent of NO). In HD patients, SkBF41 was assessed on two successive HD sessions, once immediately before and once immediately after HD. Plasma ADMA was assayed simultaneously with MS/MS (tandem MS). In the Control group, SkBF41 was determined twice, on two different days, and plasma ADMA was assayed once. In HD patients, SkBF41 was identical before (82.2+/-13.1%) and after (82.7+/-12.4%) HD, but was lower than in controls (day 1, 89.6+/-6.1; day 2, 89.2+/-6.9%; P<0.01 compared with the HD group). In contrast, plasma ADMA was higher before (0.98+/-0.17 micromol/l) than after (0.58+/-0.10 micromol/l; P<0.01) HD. ADMA levels after HD did not differ from those obtained in controls (0.56+/-0.11 micromol/l). These findings show that HD patients have impaired NO-dependent vasodilation in forearm skin, an abnormality not acutely reversed by HD and not explained by ADMA accumulation.

Dimethylarginines ADMA and SDMA: The Real Water-Soluble Small Toxins?

“…17 However, more recent clinical studies have shown a significant decrease in blood levels of ADMA. 18,19 One explanation for the conflicting results may be the result of the protein binding of ADMA, 20 however, even the extracorporeal liver support system Prometheus TM (Fresenius Medical Care, Germany), which allows the removal of protein-bound toxins, decreased ADMA by only 25%, 21 further highlighting the metabolic pathways for controlling ADMA levels.…”

Assessment of microvascular reactivity and oxidative stress in hypertensive adolescents and hemodialysis patients

“…Even if these findings are in agreement with previous observations [52,56,[95][96][97], the mechanisms of these alterations and their possible relationship have not been fully elucidated.…”

“…The within-subject variabilities determined at fixed skin sites of healthy young subjects were 15-25% for both iontophoretic and local thermal provocations in our laboratory. In order to validate the modified LDF protocol in the clinical setting, the microvascular reactivities of 12 HD patients were assessed as the presence of an impaired microvascular function had previously been demonstrated in this group [95][96][97]. In agreement with the literature, the endothelium-dependent and -independent vasodilation both proved to be markedly diminished as compared with those in healthy young subjects (p<0.001 vs the controls; data not published) ( Table 1).…”

“…The skin microvascular reactivity, as measured by means of the laser Doppler technique, has been reported to correlate with other methods applied to assess the vascular function in distinct vascular beds, including brachial artery FMD [92,93] and transthoracic coronary echocardiography [94]. The functional impairment of the microvascular system in HD affects both the endothelium-dependent [95][96][97] and -independent vasodilations [96,97]. In contrast, only the endothelium-dependent microvascular reactivity is affected in adult hypertension, as…”

Calcification of Heart and Vessels in Chronic Kidney Disease: Problems of Etiology and Pathogenesis

“…Згідно з даними Meyer і співавт. [85], один сеанс ГД погіршував ендотелійзалежну ва-зодилатацію; в інших працях -остання не змінювалась [86] або покращувалась [87]. Вміст стабільних метаболітів NO після сеан-су ГД змінювався [88][89][90], а дослідження, прис вячені вивченню динаміки циркулюю чих ендотеліальних клітин як морфологічного маркера пошкодження ендотелію протягом ГД, поодинокі [91].…”