# Central mechanisms and novel biomarkers of the salt-sensitivity of blood pressure

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $447,699

## Abstract

ABSTRACT
The central mechanisms that cause hypertension, a public health crisis that affects 1 in 3 U.S. adults, remain
largely unknown. Our pilot data demonstrate that hypothalamic paraventricular (PVN) specific Gαi2-subunit
protein-gated pathways, which are activated in response to high salt intake by the afferent renal nerves,
modulate PVN anti-inflammatory responses and PVN parvocellular neuron evoked sympathoinhibitory and
natriuretic responses to salt-intake. Additionally, PVN specific Gαi2 protein up regulation is required to counter
salt-sensitive hypertension. Further, our pilot data suggests that GNIA2 polymorphic variance represents a
novel clinical biomarker of the salt-sensitivity of blood pressure. This application will test the overall hypothesis
that dietary sodium evoked afferent renal nerve-dependent up regulation of PVN Gαi2-subunit protein-gated
pathways augments parvocellular sympathoinhibitory responses to counter the development of salt-sensitive
hypertension and that GNAI2 polymorphic variance is a clinical biomarker of the salt-sensitivity of blood
pressure. The following Specific Aims will be conducted to test this hypothesis - Specific Aim 1: To establish
that PVN Gαi2-subunit proteins modulate PVN parvocellular sympathoinhibitory neuronal activation and
inflammation to counter the initiation of salt-sensitive hypertension. Specific Aim 2: To establish that the
afferent renal nerves stimulate PVN Gαi2-subunit protein up regulation to potentiate PVN parvocellular-
mediated sympathoinhibitory and natriuretic responses to counter the initiation of salt-sensitive hypertension.
Specific Aim 3: To establish that polymorphic variance in the GNAI2 gene is a clinical biomarker for the salt-
sensitivity of blood pressure. These studies are central to the mission of the National Heart Lung and Blood
Institute (NHLBI) and address all Goals and multiple Strategies outlined in the NHLBI Strategic Plan. These
studies directly address the 2014 NHLBI Salt in Human Health and Sickness Working Group recommendations
for 1) a need to further illuminate the biological mechanisms and pathological processes to which salt may
contribute, 2) salt-sensitive hypertension as a priority research topic and, 3) the development of standardized
protocols to determine the salt-sensitivity of blood pressure at an individual level. Our research goals will be
accomplished by a multidisciplinary collaborative research team that combines the use of salt-resistant and
salt-sensitive rat models (Aims 1 & 2) and defined salt-sensitive and salt-resistant patient samples (Aim 3) to
generate mechanistic insight and clinical relevance simultaneously. By investigating the PVN Gαi2 mediated
neural mechanisms underlying salt-sensitive hypertension and the utility of GNAI2 polymorphisms to determine
the individual salt-sensitivity of blood pressure, our innovative research strategy will define a novel dietary
sodium-sensitive mechanism that prevents the initiation of sa...

## Key facts

- **NIH application ID:** 10115791
- **Project number:** 5R01HL141406-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Richard David Wainford
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $447,699
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115791

## Citation

> US National Institutes of Health, RePORTER application 10115791, Central mechanisms and novel biomarkers of the salt-sensitivity of blood pressure (5R01HL141406-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10115791. Licensed CC0.

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