# Renal Cellular Metabolism and Hypertension

> **NIH NIH P01** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $488,669

## Abstract

PROJECT 2 PROJECT SUMMARY
 The goal of Project 2 in this PPG is to understand renal cellular metabolic mechanisms of salt-sensitive
hypertension. Recent work, including work in this project in the current cycle of PPG, has discovered a novel
role of fumarase (Fh1) and fumarate metabolism in hypertension in the Dahl salt-sensitive (SS) rat. Fumarase
primarily catalyzes the conversion of fumarate to malate in the tricarboxylic acid (TCA) cycle in mitochondria.
Fumarase enzyme activity is lower in the kidneys of SS rats than SS.13BN or Sprague-Dawley (SD) rats, and
fumarate is higher and malate is lower in the kidneys of SS rats. Transgenic over-expression of fumarase on
the background of SS rat (SSTgFh1) attenuates hypertension. Intravenous infusion of a fumarate precursor in
SS.13BN rats exacerbates hypertension. It remains unknown 1) what mechanisms mediate the effect of
fumarase-related metabolites on salt-sensitive hypertension, and 2) whether blood pressure salt-sensitivity in
humans is associated with abnormalities in intermediary metabolism. Aim 1 of the proposed study will test a
novel hypothesis that fumarase insufficiency contributes to salt-sensitive hypertension in SS rats in part by
reducing arginine regeneration and nitric oxide (NO) levels in the kidney. Aim 2 studies are designed to identify
metabolites associated with blood pressure in humans on low- or high-sodium intake. The proposed study could
provide novel insights into the mechanisms by which fundamental metabolism contributes to hypertension. In
addition, it could identify specific metabolic intermediaries that might be important for mediating the effect of
dietary salt intake on blood pressure in humans.

## Key facts

- **NIH application ID:** 9841975
- **Project number:** 5P01HL116264-08
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** MINGYU LIANG
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $488,669
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841975

## Citation

> US National Institutes of Health, RePORTER application 9841975, Renal Cellular Metabolism and Hypertension (5P01HL116264-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9841975. Licensed CC0.

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