Summary of Study ST000631

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000457. The data can be accessed directly via it's Project DOI: 10.21228/M8060Z This work is supported by NIH grant, U2C- DK119886.

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Study IDST000631
Study TitleTCA Cycle Metabolites of Dietary Salt Effects on Blood Pressure in Rat Urine (part IV)
Study SummaryWe propose to analyze kidney tissue extract and urine samples from SS and SS.Fh1+ transgenic rats in addition to the analysis of urine samples from the DASH2 trial. The analysis of the rat samples will be highly valuable for several reasons. First, it will to take the findings in human subjects back to animal models and prepare us for further mechanistic studies. We hypothesize at least some of the effects of dietary salt intake on metabolite profiles in human will be recapitulated or altered in the SS rat. If this is confirmed, we will have a highly informative animal model ready for mechanistic studies in which we can investigate the functional contribution of specific metabolites to hypertension and the mechanisms involved. Second, the rat study will allow us to take advantage of a new and unique transgenic SS.Fh1+ model that we recently developed that overexpresses fumarase (Fh1) on the genetic background of the SS rat. Fumarase is a TCA cycle enzyme previously implicated in salt-induced hypertension in SS rats.
Institute
Mayo Clinic
Last NameLiang
First NameMingyu
AddressMedical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
Emailmliang@mcw.edu
Phone414-955-8539
Submit Date2017-06-23
Analysis Type DetailGC-MS
Release Date2019-07-17
Release Version1
Mingyu Liang Mingyu Liang
https://dx.doi.org/10.21228/M8060Z
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000457
Project DOI:doi: 10.21228/M8060Z
Project Title:Metabolomic Mechanisms of Dietary Salt Effects on Blood Pressure
Project Summary:Enhanced sensitivity of blood pressure to salt intake is observed in approximately 50% of hypertensive patients, reaching 75% in African American hypertensive patients. We recently discovered a novel role of abnormal cellular intermediary metabolism in hypertension in the Dahl salt-sensitive (SS) rat, the most commonly used polygenic, hereditary model of human salt-sensitive hypertension. We propose to test the hypothesis that blood pressure sensitivity to dietary salt intake in human is associated with metabolite changes in the urine. Leveraging the expertise and resources at the Mayo Clinic Metabolomics Resources Core, we propose to perform targeted LC/MS analysis and NMR spectra generation in urine samples obtained from a subset of subjects from the Dietary Approaches to Stop Hypertension – Sodium (DASH2) clinical trial and kidney tissue extract and urine samples from SS rats and a newly generated transgenic rat that overexpresses fumarase (SS.Fh1+). The study will be the first to systematically characterize urinary metabolite profiles associated with blood pressure response to salt in humans. The study is anticipated to generate new insight into the mechanisms (particularly renal mechanisms) underlying salt-sensitive hypertension. Findings of the proposed study could lead to an expanded clinical study as well as mechanistic studies in animal models.
Institute:Mayo Clinic
Last Name:Liang
First Name:Mingyu
Address:Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
Email:mliang@mcw.edu
Phone:414-955-8539

Subject:

Subject ID:SU000654
Subject Type:Rat
Subject Species:Rattus norvegicus
Taxonomy ID:10116
Species Group:Mammal

Factors:

Subject type: Rat; Subject species: Rattus norvegicus (Factor headings shown in green)

mb_sample_id local_sample_id Time point
SA035345ms5952-157 day HS
SA035346ms5952-147 day HS
SA035347ms5952-137 day HS
SA035348ms5952-167 day HS
SA035349ms5952-297 day HS
SA035350ms5952-277 day HS
SA035351ms5952-287 day HS
SA035352ms5952-127 day HS
SA035353ms5952-307 day HS
SA035354ms5952-117 day HS
SA035355ms5952-347 day HS
SA035356ms5952-357 day HS
SA035357ms5952-367 day HS
SA035358ms5952-327 day HS
SA035359ms5952-337 day HS
SA035360ms5952-107 day HS
SA035361ms5952-97 day HS
SA035362ms5952-317 day HS
SA035363ms5952-25Control
SA035364ms5952-26Control
SA035365ms5952-24Control
SA035366ms5952-19Control
SA035367ms5952-6Control
SA035368ms5952-7Control
SA035369ms5952-5Control
SA035370ms5952-4Control
SA035371ms5952-2Control
SA035372ms5952-3Control
SA035373ms5952-8Control
SA035374ms5952-17Control
SA035375ms5952-21Control
SA035376ms5952-22Control
SA035377ms5952-20Control
SA035378ms5952-1Control
SA035379ms5952-18Control
SA035380ms5952-23Control
Showing results 1 to 36 of 36

Collection:

Collection ID:CO000648
Collection Summary:Samples are from Transgenic fumerase rats and WT littermates, 13 weeks of age, placed on low salt or high salt dyets. We are interested in any differences in the TCA and AA intermediates.
Sample Type:Urine

Treatment:

Treatment ID:TR000668
Treatment Summary:We will analyze kidney tissue extract and urine samples from SS rats and the newly generated SS.Fh1+ transgenic rats. The SS.Fh1+ rat was generated using a Sleeping Beauty transposon-mediated transgenic technique. Overexpression of fumarase has been confirmed in SS.Fh1+ rats. Preliminary study indicated that the development of salt-induced hypertension was altered in SS.Fh1+ rats compared to wild-type littermate SS rats. We will analyze kidney tissue extract and urine samples collected from rats maintained on a 0.4% NaCl diet or switched to a 4% NaCl diet for 7 days. The dietary protocol has been used in numerous studies to examine mechanisms underlying salt sensitivity including early responses (7 days) to salt in the SS model. In total, 64 rat samples (two rat strains, two salt levels, and 8 rats per condition) will be analyzed.

Sample Preparation:

Sampleprep ID:SP000661
Sampleprep Summary:Rat urine TCA concentrations

Combined analysis:

Analysis ID AN000963
Analysis type MS
Chromatography type GC
Chromatography system Agilent 7890A
Column Agilent HP5-MS (30m × 0.25mm, 0.25 um)
MS Type EI
MS instrument type Single quadrupole
MS instrument name Agilent 5975C
Ion Mode POSITIVE
Units uM

Chromatography:

Chromatography ID:CH000688
Instrument Name:Agilent 7890A
Column Name:Agilent HP5-MS (30m × 0.25mm, 0.25 um)
Chromatography Type:GC

MS:

MS ID:MS000858
Analysis ID:AN000963
Instrument Name:Agilent 5975C
Instrument Type:Single quadrupole
MS Type:EI
Ion Mode:POSITIVE
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