Trimethylamine-n-oxide acutely increases cardiac muscle contractility.

TRIMETHYLAMINE-N-OXIDE ACUTELY INCREASES CARDIAC MUSCLE CONTRACTILITY. Am J Physiol Heart Circ Physiol. 2020 Apr 03;: Authors: Oakley CI, Vallejo JA, Wang D, Gray MA, Tiede-Lewis LM, Shawgo T, Daon E, Zorn G, Stubbs JR, Wacker MJ Abstract Cardiovascular disease is a major cause of morbidity and mortality among patients with chronic kidney disease (CKD). Trimethylamine-N-oxide (TMAO), a uremic metabolite that is elevated in the setting of CKD, has been implicated as a nontraditional risk factor for cardiovascular disease. While association studies have linked elevated plasma levels of TMAO to adverse cardiovascular outcomes, its direct effect on cardiac and smooth muscle function remains to be fully elucidated. We hypothesized that pathological concentrations of TMAO would acutely increase cardiac and smooth muscle contractility. These effects may ultimately contribute to cardiac dysfunction during CKD. High levels of TMAO significantly increased paced, ex vivo human cardiac muscle biopsy contractility (P
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research

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High circulating trimethylamine-N-oxide (TMAO) is associated with an increased risk of cardiovascular disease and mortality in people with chronic kidney disease (CKD). In individuals with CKD, reduced kidney function leads to decreased excretion of TMAO, which results in accumulation in the circulation. Higher circulating TMAO has been linked to higher intake of animal-based foods in omnivorous diets. Thus, plant-based diets have been suggested as an intervention to slow the progression of CKD and reduce cardiovascular risk, perhaps explained in part by reduced TMAO production.
Source: Journal of Renal Nutrition - Category: Urology & Nephrology Authors: Tags: Review Article Source Type: research
In this study, 69 patients undergoing outpatient dialysis were enrolled. Enzyme-linked immunosorbent assay was used to quantitate the baseline plasma TMAO levels in patients. The patients were divided into a high TMAO level group (TMAO ≥ 15 μmol/L) and a low TMAO level group (TMAO
Source: Renal Failure - Category: Urology & Nephrology Tags: Ren Fail Source Type: research
In this study, we validated a method to simultaneously measure urine TMA and TMAO concentrations by liquid chromatography–mass spectrometry (LC/MS). Urine TMA and TMAO can be extracted by hexane/butanol under alkaline pH and transferred to the aqueous phase following acidification for LC/MS quantitation. Importantly, during sample processing, none of the nutrients with a chemical structure containing a TMA moiety were spontaneously cleaved to yield TMA. Moreover, we demonstrated that the acidification of urine prevents an increase of TMA after prolonged storage as was observed in non-acidified urine. Finally, her...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Abstract Although substantial evidence suggests that an increase in the level of trimethylamine-N-oxide (TMAO) is associated with the risk of cardiovascular diseases, including atherosclerosis, chronic kidney diseases, and hypertension, the direct effect of TMAO on vascular endothelial function remains unclear. Therefore, we investigated the acute effects of TMAO on endothelium-dependent relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries and femoral arteries of rat. In endothelium-intact preparations, it was observed that TMAO (300 µmol/L for 60 min) did not affect AC...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research
CONCLUSIONS: This study for the first time demonstrates that TMAO promotes vascular calcification through activation of NLRP3 inflammasome and NF-κB signals, suggesting the potential link between gut microbial metabolism and vascular calcification. Reducing the levels of TMAO could become a potential treatment strategy for vascular calcification in chronic kidney disease. PMID: 31941382 [PubMed - as supplied by publisher]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - Category: Cardiology Authors: Tags: Arterioscler Thromb Vasc Biol Source Type: research
ConclusionsThe level of pCS and IS in CSF of PD is higher than expected, based on their blood level. It can influence pathogenesis and progression of PD.Graphical abstract
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research
CONCLUSIONS: The level of pCS and IS in CSF of PD is higher than expected, based on their blood level. It can influence pathogenesis and progression of PD. PMID: 31726035 [PubMed - as supplied by publisher]
Source: International Journal of Clinical Chemistry - Category: Chemistry Authors: Tags: Clin Chim Acta Source Type: research
Chronic kidney disease (CKD) affects 10-15% of the population worldwide, results in high morbidity and mortality, and requires costly treatment and renal replacement therapy. Glomerulosclerosis, tubulointerstitial fibrosis, and persistent intestinal flora disturbance are common in CKD. Short-chain fatty acids (SCFAs), produced by the intestinal microbiota, have been previously reported to ameliorate kidney injury; however, the specific concentrations and types that required to improve renal function remain unknown. The present study aim to evaluate the levels of SCFAs in healthy and CKD patients, and to test the hypothesis...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research
ConclusionAlthough the metabolic picture is complex, we suggest oxidative stress, the gut-kidney axis, acid –base balance, and energy metabolism as promising areas for future investigation.
Source: Metabolomics - Category: Biology Source Type: research
AbstractBackgroundHyperphosphatemia control is a major issue in hemodialysis patients. Both sevelamer and nicotinamide are prescribed for this purpose. In addition, they exert pleiotropic effects such as an improvement of inflammatory status and potentially enhanced clearance of uremic toxins. In the present secondary analysis of the NICOREN trial, we investigated the impact of sevelamer and nicotinamide on uremic toxins, toxin precursors, and endotoxemia in chronic hemodialysis patients.MethodsCirculating uremic toxins (including phenylacetylglutamine, trimethylamine-N-oxide, p-cresyl sulfate, indoxyl sulfate, kynurenine,...
Source: Drugs - Category: Drugs & Pharmacology Source Type: research
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