# Renal Mechanisms in Blood Pressure Control

> **NIH NIH P01** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $2,324,678

## Abstract

OVERALL PROJECT SUMMARY
The overarching goal of this PPG is to understand the role of the kidney in the pathogenesis of hypertension, a
major cause of global mortality and a primary modifiable risk factor for renal, cardiovascular and cerebrovascular
disease. Approximately half of all hypertensive subjects demonstrate sodium-sensitivity of blood pressure, the
mechanisms of which are poorly understood. Several important discoveries from the investigators of this program
provide unique conceptual insight into the development of salt-sensitive hypertension and renal damage and
form the basis for this proposal. The integrated hypothesis of our program is that salt-induced hypertension
proceeds in two phases. An initial, or primary, increase in blood pressure (BP) is followed by a more dramatic,
secondary rise of BP that is dependent upon the initial increase in renal perfusion pressure (RPP) and culminates
in `malignant hypertension' and renal end-organ damage. This global hypothesis will be tested in three projects
which are exploring previously unrecognized areas of importance in hypertension. One entirely new area of
research, to be examined in Project 1, is focused around the mechanisms of action of mTOR pathways in salt-
sensitive hypertension and the potential therapeutic use of mTOR inhibition as a novel therapeutic strategy to
treat hypertension. Project 2 is testing the innovative hypothesis that alterations in cellular metabolism,
specifically insufficiencies in fumarase-related metabolism in the kidney, contribute to hypertension by
decreasing arginine regeneration and nitric oxide levels. Project 3 is based upon the unique observation made
in the current PPG indicating that an initial elevation in renal perfusion pressure is necessary to mediate the
infiltration of immune cells into the kidney which amplifies the disease process; the proposed experiments will
elucidate the molecular transduction of this physical force. To facilitate this important work, the projects are
supported by an administrative core (Core A), and two scientific cores, which have been specially designed to
meet the needs of the program and facilitate an economy of resources. Core B will supply the unique genetic
animal models which have been generated to address the particular hypotheses of the scientific projects. Core
C will provide many of the unique scientific approaches that will be used in the projects. Together, the three
integrated projects and three cores of this PPG will provide important new information and insight into the
mechanisms of salt-sensitive hypertension in a collaborative research effort that will accelerate the acquisition
of knowledge more effectively than a simple aggregate of research projects that have no interaction or thematic
integration.

## Key facts

- **NIH application ID:** 9841969
- **Project number:** 5P01HL116264-08
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Allen W Cowley
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,324,678
- **Award type:** 5
- **Project period:** 2013-09-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841969

## Citation

> US National Institutes of Health, RePORTER application 9841969, Renal Mechanisms in Blood Pressure Control (5P01HL116264-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9841969. Licensed CC0.

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