Summary of Study ST000639
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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST000639 |
| Study Title | Neuromodulator Metabolites of Dietary Salt Effects on Blood Pressure in Rat Urine and Kidney Tissue (part XII) |
| Study Summary | We 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 Name | Liang |
| First Name | Mingyu |
| Address | Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226 |
| mliang@mcw.edu | |
| Phone | 414-955-8539 |
| Submit Date | 2017-06-23 |
| Analysis Type Detail | LC-MS |
| Release Date | 2019-07-17 |
| Release Version | 1 |
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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: | SU000662 |
| 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 | Sample ID | grouping |
|---|---|---|---|
| SA035999 | ms6105-1 | YCR1 urine | Transgenic Het |
| SA036000 | ms6105-2 | YCR2 urine | Transgenic Negative |
| SA036001 | ms6105-3 | YCR3 urine | Transgenic Negative |
| SA036002 | ms6105-4 | YCR4 urine | Transgenic Negative |
| SA036003 | ms6105-5 | YCR5 urine | Transgenic Het |
| SA036004 | ms6105-6 | YCR6 urine | Transgenic Negative |
| SA036005 | ms6105-7 | YCR7 urine | Transgenic Het |
| SA036006 | ms6105-8 | YCR8 urine | Transgenic Het |
| Showing results 1 to 8 of 8 |
Collection:
| Collection ID: | CO000656 |
| 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: | Kidney |
Treatment:
| Treatment ID: | TR000676 |
| 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: | SP000669 |
| Sampleprep Summary: | Rat urine and kidney tissue extract (outer medulla and cortex) neuromodulators concentrations. Only urine results. |
Combined analysis:
| Analysis ID | AN000971 |
|---|---|
| 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: | CH000696 |
| Instrument Name: | Waters Acquity |
| Column Name: | Waters Acquity BEH C18 (150 x 2.1mm,1.7um) |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS000866 |
| Analysis ID: | AN000971 |
| Instrument Name: | Thermo Quantum Ultra |
| Instrument Type: | Triple quadrupole |
| MS Type: | ESI |
| Ion Mode: | POSITIVE |
