Effects of Uremic Plasma on α- and β-Adrenoceptor Subtypes

Ferchland, A; Rettkowski, O; Pönicke, Klaus; Deuber, H. J.; Osten, B; Brodde, Otto‐Erich

doi:10.1159/000045124

Cited by 9 publications

(3 citation statements)

References 20 publications

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“…In adult Nx rats, Leineweber et al [5] observed downregulation of LV β receptors but not right ventricular receptors. Downregulation of β-adrenergic receptors seen in this study can partially explain the β-adrenoceptor hypo-responsiveness seen in uremic patients and rats [5,43].…”

Section: Discussionmentioning

confidence: 92%

Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system

et al. 2009

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Cardiac hypertrophy is frequently encountered in patients with renal failure and represents an independent risk factor for cardiovascular morbidity and mortality. The pathogenesis of cardiac hypertrophy is related to multiple factors, including excess adrenergic activity. This study investigated how renal injury in the early stages of life affects the adrenergic system and thereby potentially influences cardiac growth. Biomarkers of cardiac hypertrophy were used to assess adrenergic function. Newborn male Sprague-Dawley rats were allocated to three groups of five rats each: 5/6 nephrectomy (Nx), pair-fed controls (PF), and sham-operated (SH). Nx animals had significantly higher plasma urea nitrogen, serum creatinine, and mean arterial blood pressure. The heart-weight/body-weight ratio of the Nx cohort was higher than SH and PF (p < 0.001) groups. Plasma norepinephrine (NE) of Nx animals was almost twofold higher than SH and PF (p < 0.01) animals. Compared with SH and PF, Nx animals had higher alpha1A-receptor protein expression, lower cardiac beta1- and beta2-receptor protein expression (p < 0.05), but higher G-protein-coupled receptor kinase-2 (GRK2) expression (p < 0.05). Norepinephrine transporter protein (NET) and renalase protein expression in cardiac tissue from Nx pups were significantly lower than SH and PF. Our data suggest that early age Nx animals have increased circulating catecholamines due to decreased NE metabolism. Enhancement of cardiac GRK2 and NE can contribute to cardiac hypertrophy seen in Nx animals. Furthermore, AKT (activated via alpha1A receptors), as well as increased alpha1A receptors and their agonist NE, might contribute to the observed hypertrophy.

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Section: Discussionmentioning

confidence: 92%

Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system

et al. 2009

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“…Decreased responses and densities of β2-adrenoceptors have been reported in CRF patients [ 33 ]. In addition, uremic patients have significantly decreased β1-and β2-adrenoceptors [ 34 ]. It is also worth noting that in rats rendered uremic by partial nephrectomy.…”

Section: Discussionmentioning

confidence: 99%

Melatonin receptor 1A gene polymorphism rs13140012 and serum melatonin in atherosclerotic versus non-atherosclerotic Egyptian ESRD patients: pilot study

Aghoury

Tayae

Kholy

et al. 2020

Heliyon

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Aim To study the relationship between melatonin levels and Melatonin membrane receptor 1A ( MTNR1A ) SNP (rs13140012) in end-stage renal disease patients (ESRD) in Alexandria, Egypt on maintenance hemodialysis with or without atherosclerosis. Materials and methods 40 end-stage renal disease patients on regular hemodialysis were divided into 2 subgroups, one with (n = 20) and one without atherosclerosis (n = 20) and normal subjects (n = 40). Serum melatonin, carotid intimal medial thickness (CIMT) were measured. Melatonin membrane receptor 1A ( MTNR1A ) SNP (rs13140012) genotyping was done using 5'nuclease Allelic discrimination. Results Serum melatonin was significantly lower in ESRD patients [1.6 to 11.30 (pg/mL) with a median of 2.5] than the control group [20.50 to 56.40 (pg/mL) with a median of 35.20]. Serum melatonin was significantly lower in atherosclerotic patients subgroup [1.6–2.50 (pg/mL) with a median value of 2.30] than non-atherosclerotic patients subgroup [2.0–11.30 (pg/mL) with a median of 4.9]. No significant association was found between serum melatonin and ( MTNR1A ) SNP (rs13140012) (p = 0.633). Conclusion These results lead us to suggest that melatonin production is impaired in ESRD patients (included in this pilot study), and this impairment is more evident in atherosclerotic ESRD patients.

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“…Several studies documented a sympathetic overstimulation (reviewed in [12]) in dialysis patients that reduces the expression of adrenoceptors on target cells in addition to uremia that reduces the expression of ß-adrenoceptors [13] itself. The function of the parasympathetic axis is less well studied.…”

Section: Introductionmentioning

confidence: 99%

Association between autonomic nervous dysfunction and cellular inflammation in end-stage renal disease

Seibert

Zohles

Ulrich

et al. 2016

BMC Cardiovasc Disord

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BackgroundAlterations in autonomic nervous function are common in hemodialysis (HD) patients. Sympathetic as well as parasympathetic activation may be associated with immune and inflammatory responses. We intended to confirm a role of autonomous dysregulation for inflammation in HD patients.Methods30 HD patients (including 15 diabetics) and 15 healthy controls were studied for heart rate variability (HRV) using 5 min ECG recordings. Heart rate variability was estimated by time-domain parameters (the standard deviation of the RR intervals (SDNN) and the percentage of pairs of adjacent RR intervals differing by >50 ms (pNN50)) and frequency-domain-analysis (high- and low-frequency variation of RR intervals, HF and LF). Inflammation was detected as serum C-reactive Protein (CRP), IL-6 and circulating monocyte subpopulation numbers. Immune cells were characterized by ACh receptor expression.ResultsPatients differed from controls in terms of age (68.0 [14.8] yrs vs. 58.0 [13.0] yrs, p < 0.001; Median [IQR]) and sex. However, HRV parameters were different in controls and HD patients (SDNN controls 34.0 [14.0] ms, HD patients 15.5 [14.8] ms, p < 0.01). This finding was not restricted to patients with diabetes mellitus (diab), although diabetes is an important cause of autonomous dysfunction (SDNN, diab 13.0 [14.0] ms, non-diab 18.0 [15.3] ms, p = 0.8). LF and HF were reduced by the same magnitude to 1/3 of those in controls. Patients suffered from chronic inflammation (CRP 9.4 [12.9] mg/l, controls 1.6 [2.4] mg/l, p < 0.001) and expanded proinflammatory monocyte subpopulations (CD14++/CD16+ cells: patients 41 [27]/μl, controls 24 [18]/μl, p < 0.01). ECG parameters did not correlate with inflammation in patients, but monocyte ACh receptor expression was enhanced, indicating potentially elevated responsiveness of this cell type to parasympathetic regulation.ConclusionsHD patients have strongly impaired HRV. Chronic inflammation is not related to autonomous dysfunction, although monocytes express the ACh receptor at enhanced density making them potentially more sensitive to parasympathetic effects.Trial registrationThis study was listed with ClinicalTrials.gov (NCT00878033).Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0385-1) contains supplementary material, which is available to authorized users.

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Effects of Uremic Plasma on α- and β-Adrenoceptor Subtypes

Cited by 9 publications

References 20 publications

Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system

Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system

Melatonin receptor 1A gene polymorphism rs13140012 and serum melatonin in atherosclerotic versus non-atherosclerotic Egyptian ESRD patients: pilot study

Association between autonomic nervous dysfunction and cellular inflammation in end-stage renal disease

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