Impaired resistance artery function in patients with end-stage renal disease.
ABSTRACT We investigated an effect of uraemia on structural and functional features of human resistance vasculature. Arteries (≈ 200 μm) isolated from subcutaneous fat biopsies obtained from 35 ESRD (end-stage renal disease) patients starting peritoneal dialysis and 30 matched controls were studied using isolated small artery bioassays. Flow-mediated dilatation was attenuated in ESRD patients compared with controls. NO (nitric oxide) contribution to flow was lacking in ESRD patients, but present in the controls. ADMA (asymmetrical dimethyl L-arginine) levels were higher in the ESRD group compared with the control group. Dilatation in response to acetylcholine was reduced in ESRD patients compared with controls, but response to NO donor was similar. Expression of nitrotyrosine and heat shock proteins 70 and 27, but not 90, was increased in arteries from ESRD patients compared with controls. Arterial remodelling was absent in ESRD patients. There was no difference between the groups in myogenic tone, vascular reactivity or sensitivity to several vasoconstrictors. Arterial distensibility, reflecting passive properties of the vascular wall, was reduced in ESRD patients compared with controls. Exclusion of ESRD patients with diabetes and/or cardiovascular disease from analyses had no influence on the main findings. Thus we propose that uraemia has a strong impact on endothelial function and passive properties of the arterial wall of human peripheral resistance vasculature. The reduced contribution of NO to flow stimulus via enhanced nitrosative stress and higher plasma concentrations of ADMA may suggest potential mechanisms behind endothelial dysfunction in the resistance peripheral circulation in ESRD.
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ABSTRACT: Cardiovascular disease is the leading cause of death in patients with end stage renal disease (ESRD). The vasodilator mechanisms in small resistance arteries are in earlier studies shown to be reduced in patients with end stage renal disease. We studied whether endothelium dependent vasodilatation were diminished in ESRD patients and the interaction between the macro- and microcirculation. Eleven patients with ESRD had prior to renal transplant or insertion of peritoneal dialysis catheter measured pulse wave velocity. During surgery, a subcutaneous fat biopsy was extracted. Resistance arteries were then dissected and mounted on a wire myograph for measurements of dilator response to increasing concentrations of acetylcholine after preconstriction with noradrenaline. Twelve healthy kidney donors served as controls. Systolic blood pressure was elevated in patients compared to the healthy controls; no difference in the concentration of asymmetric dimethyl arginine was seen. No significant difference in the endothelium dependent vasodilatation between patients and controls was found. Correlation of small artery properties showed an inverse relationship between diastolic blood pressure and nitric oxide dependent vasodilatation in controls. Pulse pressure was positively correlated to the total endothelial vasodilatation in patients. A negative association between S-phosphate and endothelial derived hyperpolarisation-like vasodilatation was seen in resistance arteries from controls. This study finds similar vasodilator properties in kidney patients and controls. However, correlations of pulse pressure and diastolic blood pressure with resistance artery function indicate compensating measures in the microcirculation during end stage renal disease.PLoS ONE 01/2014; 9(4):e94638. · 3.53 Impact Factor
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ABSTRACT: Chronic kidney disease (CKD), characterized by senile inflammation, is a risk factor for cardiovascular disease. Conduit artery function and small artery structure relate to cardiovascular disease. We examined the correlations, determinants and interrelationships of arterial indices in association with CKD in a cross-sectional study of 139 patients (60% male; mean age 44 years) with CKD (stages 3-5, 39%) who underwent a renal biopsy. Conduit artery function and small artery sclerosis were assessed by brachial artery flow-mediated dilatation (FMD) and semiquantitative evaluation of small artery intimal thickening (SA-IT), respectively. The estimated glomerular filtration rate correlated with FMD (r=0.31, P=0.0002) and inversely correlated with SA-IT (r=-0.54, P<0.0001). Multiple regression analysis showed that FMD was inversely correlated with SA-IT and vice versa. In addition, high-sensitivity C-reactive protein (hs-CRP) was significantly correlated with SA-IT, but not FMD. Multiple logistic analysis revealed that higher hs-CRP concomitant with decreased FMD was further associated with the risk of severe SA-IT compared with their individual effects. These findings suggest that both conduit artery and small artery disease develop with mutual interaction in parallel with decreased kidney function. Coexistence of inflammation and conduit artery dysfunction may be closely related to renal small artery sclerosis in patients with CKD.Hypertension Research advance online publication, 20 March 2014; doi:10.1038/hr.2014.60.Hypertension Research 03/2014; · 2.79 Impact Factor
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ABSTRACT: G-protein-coupled estrogen receptors (GPERs) have been proposed to mediate estrogen-mediated vasodilation. The presence of GPER-dependent vasodilation in human resistance-sized arteries (HRAs) or its signal transduction pathways have not been investigated. HRAs in subcutaneous fat tissues (biopsies from postmenopausal women (PMW), age-matched men (M) and pregnant women (PGW)) were mounted for in vitro isometric force recording. Vasodilation induced by G-1 (selective GPER- agonist, 3 μM) from HRAs pre-contracted with norepinephrine amounted to 40 ± 5% in PMW, significantly larger than those obtained from M (20 ± 5%) or PGW (20 ± 5%). L-NAME (nitric oxide (NO) synthase inhibitor) abolished these relaxations in PGW, attenuated them in PMW and had no effect in M. Immunohistochemical analysis confirmed the presence of GPER in both smooth muscle and endothelial cells of HRA with maximum expression in PGW. In cultured human umbilical vein endothelial cells (HUVECs), G-1 increased NO-synthesis concentration-dependently through higher expressions of endothelial NO-synthase (eNOS) and through enhanced phosphorylation of eNOS on Ser1177. In conclusion, GPER vasodilates human resistance arteries through various activating mechanisms of the eNOS-signaling pathway.Maturitas 01/2014; · 2.84 Impact Factor