Summary of study ST000632

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 IDST000632
Study TitleAmino Acid Metabolites of Dietary Salt Effects on Blood Pressure in Rat Urine (part V)
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 DetailLC-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:SU000655
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
SA035381ms5953-157 day HS
SA035382ms5953-147 day HS
SA035383ms5953-137 day HS
SA035384ms5953-167 day HS
SA035385ms5953-297 day HS
SA035386ms5953-277 day HS
SA035387ms5953-287 day HS
SA035388ms5953-127 day HS
SA035389ms5953-307 day HS
SA035390ms5953-117 day HS
SA035391ms5953-347 day HS
SA035392ms5953-357 day HS
SA035393ms5953-367 day HS
SA035394ms5953-327 day HS
SA035395ms5953-337 day HS
SA035396ms5953-107 day HS
SA035397ms5953-97 day HS
SA035398ms5953-317 day HS
SA035399ms5953-25Control
SA035400ms5953-26Control
SA035401ms5953-24Control
SA035402ms5953-19Control
SA035403ms5953-6Control
SA035404ms5953-7Control
SA035405ms5953-5Control
SA035406ms5953-4Control
SA035407ms5953-2Control
SA035408ms5953-3Control
SA035409ms5953-8Control
SA035410ms5953-17Control
SA035411ms5953-21Control
SA035412ms5953-22Control
SA035413ms5953-20Control
SA035414ms5953-1Control
SA035415ms5953-18Control
SA035416ms5953-23Control
Showing results 1 to 36 of 36

Collection:

Collection ID:CO000649
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:TR000669
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:SP000662
Sampleprep Summary:Rat urine amino acids

Combined analysis:

Analysis ID AN000964
Analysis type MS
Chromatography type Reversed phase
Chromatography system Waters Acquity
Column Waters Acquity BEH C18 (150 x 2.1mm, 1.7um)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name Thermo Quantum Ultra
Ion Mode POSITIVE
Units uM

Chromatography:

Chromatography ID:CH000689
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (150 x 2.1mm, 1.7um)
Chromatography Type:Reversed phase

MS:

MS ID:MS000859
Analysis ID:AN000964
Instrument Name:Thermo Quantum Ultra
Instrument Type:Triple quadrupole
MS Type:ESI
Ion Mode:POSITIVE
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