# Mitochondria-Mediated Effects and Therapeutic Potential of Atrial Natriuretic Peptide in Salt-Sensitive Hypertension Diversity Supplement

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $26,968

## Abstract

PROJECT SUMMARY
There is no specific treatment available for the subpopulation of patients with salt sensitivity of blood pressure
(BP); unfortunately, the molecular mechanisms underlying salt-sensitivity remain poorly understood. One of the
major proposed mechanisms for the development of salt-sensitive (SS) hypertension involves a defect in the
ability of the kidneys to excrete salt. Atrial Natriuretic Peptide (ANP) encoded by Nppa, is a hormone known to
promote salt excretion and BP reduction. There are clinical data implicating inherently low levels of ANP in the
development of SS hypertension. Among other effects, ANP (via cGMP-related mechanisms) is known to be
beneficial for mitochondrial bioenergetics and biogenesis. However, there is a gap in knowledge regarding the
effects of ANP on mitochondria in the kidney, especially in SS hypertension. Our overarching hypothesis of the
parent project is that in SS hypertension ANP deficiency/reduced sensitivity to ANP is causative to renal
mitochondrial dysfunction and associated sodium transport imbalance. To address the central hypothesis of the
parent proposal, we developed three specific aims: Aim 1. Establish whether increased ANP levels are beneficial
for renal salt handling and cardiac function in SS hypertension. Aim 2. Determine whether low renal cGMP level
resulting from lack of ANP causes an increase in renal mitochondrial Ca2+ and reactive oxygen species (ROS).
Aim 3. Test the hypothesis that disrupted Ca2+ balance and excessive ROS production by dysfunctional
mitochondria affect renal sodium handling in SS hypertension. From these proposed aims Dr. Spires and Dr.
Ilatovskaya derived additional aims focused on studying the effects of ANP in SS hypertension in the context of
glomerular function and injury specifically. For the focus of this supplemental project the aims are as follows:
Suppl. Aim 1. To determine the physiological effects of ANP on glomerular function and injury in SS
hypertension. Suppl. Aim 2. To analyze the effects of Nppa knockout on podocyte calcium handling and
mitochondrial function in SS hypertension. Dr. Spires and Dr. Ilatovskaya put together a very strong team of
mentors and collaborators to aid in completion of these Aims, and the methodological training of Dr. Spires during
the Supplement will be combined with a rigorous career development program. The successful completion of
the proposed studies in the parent proposal as well as the those proposed for this supplemental award will
unravel the novel cause-effect mechanisms of salt-sensitivity.

## Key facts

- **NIH application ID:** 10337412
- **Project number:** 3R01HL148114-01A1S1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Daria Ilatovskaya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $26,968
- **Award type:** 3
- **Project period:** 2020-08-14 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337412

## Citation

> US National Institutes of Health, RePORTER application 10337412, Mitochondria-Mediated Effects and Therapeutic Potential of Atrial Natriuretic Peptide in Salt-Sensitive Hypertension Diversity Supplement (3R01HL148114-01A1S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10337412. Licensed CC0.

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