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Ernst E van Faassen

Publications and source records attributed to Ernst E van Faassen.

5 recordsLinked to original sources
PubMed2006

Low albumin levels increase endothelial NO production and decrease vascular NO sensitivity.

BACKGROUND: Hypoalbuminaemia is associated with increased risk of cardiovascular disease. It is unclear whether endothelial dysfunction is a direct result of low albumin or whether it is caused by factors like chronic inflammation or dyslipidaemia. In this study, the effect of low albumin concentrations on endothelial nitric oxide synthase (eNOS)-dependent NO production was determined in vitro and ex vivo. METHODS: eNOS activity, assessed by arginine-citrulline conversion, and NO production, determined by 4,5-diaminofluorescein diacetate, electron paramagnetic resonance and Griess colorimetry, were measured in cultured endothelial cells expressing high levels of eNOS (bEnd.3) after exposure to albumin concentrations ranging from 0.5 mmol/l (33 g/l) to 0 mmol/l. Analbuminaemic and control rat plasma NO metabolites and aortic eNOS protein mass were determined, and aortic endothelium-independent and endothelium-dependent vasodilator tone were measured ex vivo under albumin-free conditions. RESULTS: In vitro, eNOS activity was significantly increased in the absence of albumin (75 +/- 2 vs 26 +/- 6 pmol/min/mg protein; P < 0.01). Low albumin levels consistently increased NO production in endothelial cells. Plasma NO metabolites were increased (18.2 +/- 1.9 vs 12.5 +/- 0.8 micromol/l; P < 0.05) and endothelium-independent relaxation was markedly blunted in analbuminaemic rats, resulting in a considerably higher ED50 (80 +/- 2 vs 1.1 +/- 0.2 nmol/l, P < 0.01), while endothelium-dependent dilatation was slightly, but significantly, increased. Aortic eNOS protein mass was not affected. This implies that in vivo hypoalbuminaemia reduces vascular NO sensitivity. CONCLUSION: We show that low albumin as such seems to enhance, rather than diminish, eNOS-mediated endothelial NO production.

Albumins↗
PubMed2006

New insights into the coordination chemistry and molecular structure of copper(II) histidine complexes in aqueous solutions.

Aqueous solutions of Cu2+/histidine (his) (1:2) have been analyzed in parallel with infrared, Raman, ultraviolet/visible/near-infrared, electron spin resonance, and X-ray absorption spectroscopy in the pH range from 0 to 10. Comprehensive interpretation of the data has been used to extract complementary structural information in order to determine the relative abundance of the different complexes. The formation of six different, partly coexisting species is proposed. Structural proposals from literature have been unambiguously confirmed, refined, or, in several cases, corrected. At highly acidic conditions, Cu2+ and his are present as free ions, but around pH = 2, coordination starts via the deprotonated carboxylic acid group. This results in the intermediate species Cu2+[H3his+(Oc)] and Cu2+[H3his+(Oc)]2. The coordination via Oc is attended with a drop in the pKa value of the other receptor groups resulting in a concomitant conversion to the bidentates Cu2+[H2his0(Oc,Nam)] and Cu2+[H2his0(Oc,Nam)]2, with the latter being dominant at pH = 3.5. Coordination of the imidazole ring begins around pH = 3 and leads to the formation of the mixed ligand complexes Cu2+[H2his0(Oc,Nam)][Hhis-(Oc,Nam,Nim)] and Cu2+[Hhis-(Nam,Nim)][Hhis-(Oc,Nam,Nim)] around pH = 5. It is demonstrated that coordination of the imidazole ring occurs predominantly via the N(pi) atom. At pH > 7, the double-tridentate ligand complex Cu2+[Hhis-(Oc,Nam,Nim)]2 is the major species with the N atoms in the equatorial plane and the O atoms in the axial position. This complex decomposes at pH > 10 into a copper oxide/hydroxide precipitate. The overall results provide a consistent picture of the mechanism that drives the coordination and complex formation of the Cu2+/his system.

Journal Article↗
PubMed2002

Anti-inflammatory effects of tetrahydrobiopterin on early rejection in renal allografts: modulation of inducible nitric oxide synthase.

Oxidative stress contributes to the development of early transplant failure. As nitric oxide synthases (NOS) can act as sources of superoxide, we investigated the effect of the NOS cofactor tetrahydrobiopterin (BH4) on oxyradical production and early rejection in a rat kidney transplantation model. Allograft transplantation (Brown Norway to Lewis) showed more renal superoxide production and monocyte infiltration when compared with isografts (Lewis to Lewis). Administration of the stable BH4 precursor sepiapterin had no effect on superoxide production in the isografts (51+/-10 vs. 69+/-17 cps/10 mg protein), but led to a marked decrease in superoxide production in the allografts (116+/-11 vs. 60+/-6 cps/10 mg protein; P<0.05) and was accompanied by a reduction in periarterial macrophage infiltration (3.3+/-0.7 vs. 1.3+/-0.3 cells/vessel; P<0.05) and an increase in NO production (78+/-22 vs. 173+/-12 AU/g kidney) (P<0.01). In vitro experiments confirm that iNOS can produce superoxide mainly from the heme domain, whereas BH4 administration can reverse this superoxide production in the presence of adequate anti-oxidant defense. Our findings support the hypothesis that BH4 can be used to modulate the function of the inflammatory iNOS isoform and suggest a potential therapeutic role for sepiapterin in early allograft rejection.

Animals↗
PubMed2001

Vitamin E alleviates renal injury, but not hypertension, during chronic nitric oxide synthase inhibition in rats.

Chronic nitric oxide (NO) synthase inhibition in rats causes hypertension, renal vascular injury, and proteinuria. NO deficiency increases superoxide (O(2)(-)) activity, but the effects of antioxidant treatment on renal injury have not been studied in this model. Exposure of rats to N omega-nitro-L-arginine (L-NNA) for 4 d markedly decreased NO-dependent relaxation in aortic rings and increased glomerular and renal interstitial monocyte influx, but renal O(2)(-) activity was not increased. After 7 d, BP and proteinuria were significantly increased. After 21 d of L-NNA treatment, rats displayed severe hypertension, decreased GFR, marked proteinuria, glomerular ischemia, renal vascular and tubulointerstitial injury, and complete loss of NO-dependent relaxation. Renal O(2)(-) activity was markedly increased [lucigenin-enhanced chemiluminescence (LEC), 279 +/- 71 versus 50 +/- 7 counts/10 mg, P < 0.01; electron paramagnetic resonance spectroscopy, 0.57 +/- 0.05 versus 0.34 +/- 0.04 U/10 mg, P < 0.05]. Apocynin, a specific inhibitor of NADPH oxidase, and diphenyleneiodonium, an inhibitor of flavin-containing enzymes, completely inhibited LEC signals in vitro, whereas allopurinol had no effect, indicating that NAD(P)H oxidase plays a major role in superoxide production in the kidney. Endothelial function remained impaired during cotreatment with alpha-tocopherol and there was no effect on hypertension or tubulointerstitial injury, but glomerular ischemia, decreases in GFR, and renal vascular injury were prevented and proteinuria was ameliorated. Renal LEC signals were intermediate between control and L-NNA-alone values (181 +/- 84 counts/10 mg). Chronic NO synthase inhibition in rats results in marked increases in renal cortical O(2)(-) activity, mediated by flavin-dependent oxidases. The absence of early increases in renal O(2)(-) activity, in the presence of endothelial dysfunction and macrophage influx, indicates that increased renal O(2)(-) activity is neither attributable to NO deficiency per se nor solely related to macrophage influx. The improvement of glomerular function and amelioration of renal vasculitis and proteinuria with vitamin E cotreatment indicate that oxidants are involved in the pathogenesis of renal injury in this model. However, markedly impaired endothelial function and unabated hypertension persist with vitamin E treatment and seem to be directly attributable to NO deficiency.

Animals↗