378 Regulation of renal function by the peroxisome proliferator-activated receptor-alpha: A novel target for treating hypertension
OBJECTIVES/GOALS: Approximately 37 million people in the U.S. have chronic kidney disease, which is a major risk factor for cardiovascular and end stage renal diseases. PPAR-αknockout (KO) mice exhibit increased renal inflammation and blood pressure. In this study, we investigated the role of PPAR-...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Cambridge University Press
2023-04-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866123004156/type/journal_article |
| _version_ | 1797840391152599040 |
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| author | Mark D Hatcher Kathryn Sandberg Dexter Lee |
| author_facet | Mark D Hatcher Kathryn Sandberg Dexter Lee |
| author_sort | Mark D Hatcher |
| collection | DOAJ |
| description | OBJECTIVES/GOALS: Approximately 37 million people in the U.S. have chronic kidney disease, which is a major risk factor for cardiovascular and end stage renal diseases. PPAR-αknockout (KO) mice exhibit increased renal inflammation and blood pressure. In this study, we investigated the role of PPAR-αin renal function in a mouse model of hypertension. METHODS/STUDY POPULATION: Male 4-month-old wild type (WT) and PPAR-αKO mice were instrumented with radio transmitters by artery canulation (Data Science Intl). This method minimizes stress and artifacts by avoiding the use of tethering, restraining, or anesthetizing the mice during data sampling. After recovery from surgery, we continuously measured mean arterial pressure (MAP) via radio telemetry in conscious ambulatory mice. After baseline MAP was established, vehicle (Veh; saline) or angiotensin II (Ang II) were infused using an osmotic minipump at a slow pressor dose (400 ng/kg/min) for 12 days. On day 12, we injected an intravenous bolus of fluorescin-sinistrin (3.74µl/g body weight) and collected 8 blood samples (20µl/sample) over 75 minutes to enable calculation of the glomerular filtration rate (GFR) using [GFR = I/(A/α+ B/ß)]. RESULTS/ANTICIPATED RESULTS: Similar to our prior observations, no significant (ns) differences in baseline MAP were observed between WT and PPAR-αKO mice [(mmHg): WT (n=6), 111 ± 20 vs. PPAR-αKO (n=6), 113 ± 10; ns] whereas after 12 days of the slow pressor effect of Ang II, MAP was increased in both strains [(mmHg): WT (n=8), 138 ± 11# vs. PPAR-αKO (n=8) , 156 ± 16#; #p DISCUSSION/SIGNIFICANCE: PPAR-αprotects mice from worsening hypertension and is critical to preserving GFR during normotensive conditions. Ongoing studies are further investigating how PPAR-αregulates renal function. These finding suggest therapeutics designed to increase PPAR-αactivity could have clinical benefit in chronic kidney disease. |
| first_indexed | 2024-04-09T16:14:20Z |
| format | Article |
| id | doaj.art-2d21d7556ced462fa3801edeeafef6e7 |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-09T16:14:20Z |
| publishDate | 2023-04-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-2d21d7556ced462fa3801edeeafef6e72023-04-24T05:55:57ZengCambridge University PressJournal of Clinical and Translational Science2059-86612023-04-01711211210.1017/cts.2023.415378 Regulation of renal function by the peroxisome proliferator-activated receptor-alpha: A novel target for treating hypertensionMark D Hatcher0Kathryn Sandberg1Dexter Lee2Georgetown-Howard UniversitiesGeorgetown UniversityHoward UniversityOBJECTIVES/GOALS: Approximately 37 million people in the U.S. have chronic kidney disease, which is a major risk factor for cardiovascular and end stage renal diseases. PPAR-αknockout (KO) mice exhibit increased renal inflammation and blood pressure. In this study, we investigated the role of PPAR-αin renal function in a mouse model of hypertension. METHODS/STUDY POPULATION: Male 4-month-old wild type (WT) and PPAR-αKO mice were instrumented with radio transmitters by artery canulation (Data Science Intl). This method minimizes stress and artifacts by avoiding the use of tethering, restraining, or anesthetizing the mice during data sampling. After recovery from surgery, we continuously measured mean arterial pressure (MAP) via radio telemetry in conscious ambulatory mice. After baseline MAP was established, vehicle (Veh; saline) or angiotensin II (Ang II) were infused using an osmotic minipump at a slow pressor dose (400 ng/kg/min) for 12 days. On day 12, we injected an intravenous bolus of fluorescin-sinistrin (3.74µl/g body weight) and collected 8 blood samples (20µl/sample) over 75 minutes to enable calculation of the glomerular filtration rate (GFR) using [GFR = I/(A/α+ B/ß)]. RESULTS/ANTICIPATED RESULTS: Similar to our prior observations, no significant (ns) differences in baseline MAP were observed between WT and PPAR-αKO mice [(mmHg): WT (n=6), 111 ± 20 vs. PPAR-αKO (n=6), 113 ± 10; ns] whereas after 12 days of the slow pressor effect of Ang II, MAP was increased in both strains [(mmHg): WT (n=8), 138 ± 11# vs. PPAR-αKO (n=8) , 156 ± 16#; #p DISCUSSION/SIGNIFICANCE: PPAR-αprotects mice from worsening hypertension and is critical to preserving GFR during normotensive conditions. Ongoing studies are further investigating how PPAR-αregulates renal function. These finding suggest therapeutics designed to increase PPAR-αactivity could have clinical benefit in chronic kidney disease.https://www.cambridge.org/core/product/identifier/S2059866123004156/type/journal_article |
| spellingShingle | Mark D Hatcher Kathryn Sandberg Dexter Lee 378 Regulation of renal function by the peroxisome proliferator-activated receptor-alpha: A novel target for treating hypertension Journal of Clinical and Translational Science |
| title | 378 Regulation of renal function by the peroxisome proliferator-activated receptor-alpha: A novel target for treating hypertension |
| title_full | 378 Regulation of renal function by the peroxisome proliferator-activated receptor-alpha: A novel target for treating hypertension |
| title_fullStr | 378 Regulation of renal function by the peroxisome proliferator-activated receptor-alpha: A novel target for treating hypertension |
| title_full_unstemmed | 378 Regulation of renal function by the peroxisome proliferator-activated receptor-alpha: A novel target for treating hypertension |
| title_short | 378 Regulation of renal function by the peroxisome proliferator-activated receptor-alpha: A novel target for treating hypertension |
| title_sort | 378 regulation of renal function by the peroxisome proliferator activated receptor alpha a novel target for treating hypertension |
| url | https://www.cambridge.org/core/product/identifier/S2059866123004156/type/journal_article |
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