# Aging and hypertension: Integrated renal and sympathetic control of blood pressure

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $615,260

## Abstract

ABSTRACT
The prevalence of hypertension, which is predicted to be the leading global cause of death and disability by the
year 2020, increases with age from 46% of U.S. adults aged 20-44 to >78% of U.S. adults above the age of
65. Less than half of elderly patients with hypertension achieve adequate blood pressure control and older
hypertensive patients are significantly less likely to receive a thiazide prescription (first line anti-hypertensive)
than younger patients. This suggests contemporary prescribing practices to the elderly are sub-optimal.
Further, the development of antihypertensive drugs has been dramatically less productive than expected,
making new mechanistic insights into age-dependent blood pressure regulation essential. This application will
test the global hypothesis that attenuated mechanosensitive afferent renal nerve sympathoinhibitory reflexes
evoke sodium chloride cotransporter-mediated renal sodium retention and age-dependent hypertension. These
studies will employ our novel technique of selective afferent renal nerve ablation, a unique in-vivo surgical
approach to activate the mechanosensitive afferent renal nerves, and genetic and pharmacological tools in 3, 8
and 16 month old Sprague-Dawley rats (model of normal aging) that exhibit age-dependent hypertension to
provide new mechanistic insight into the pathophysiology of age-dependent hypertension. The following
Specific Aims will be conducted to test this hypothesis: Specific Aim 1: Impairments in the renal sympathetic
nerves contribute to age-dependent hypertension. Specific Aim 2: Attenuation of the mechanoreceptor-
activated sympathoinhibitory afferent renal nerve natriuretic reno-renal reflex occurs in age-dependent
hypertension. Specific Aim 3: Age-dependent elevations in sympathetic tone increase NCC activity, via a NE-
α1-adrenoceptor-gated WNK1-OxSR1 signal transduction pathway, to evoke renal nerve-dependent sodium
retention and hypertension. These hypertension focused studies are central to the mission of the NIA, which is
to understand the nature of the aging processes and diseases associated with aging to extend healthy years of
life and the NHLBI, which is to promote the prevention and treatment of heart, lung and blood diseases.
Specific Aim 1 will establish an age-dependent role of the renal sympathetic nerves in sodium excretion and
blood pressure regulation during acute and chronic challenges to salt and water balance. Specific Aim 2 will
establish a key role of an impairment in sensory renal mechanoreceptor activation that reduces central
sympathoinhibitory signaling in the pathophysiology of age-dependent hypertension. Specific Aim 3 will
establish the age-dependent actions of the sympathetic nervous system to regulate the sodium chloride
cotransporter, via a novel α1- adrenoceptor signal transduction pathway. Our innovative research strategy will
define a novel age-dependent renal sympathetic nerve dependent mechanism through which sodium excretion
...

## Key facts

- **NIH application ID:** 10169220
- **Project number:** 5R01AG062515-03
- **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:** $615,260
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169220

## Citation

> US National Institutes of Health, RePORTER application 10169220, Aging and hypertension: Integrated renal and sympathetic control of blood pressure (5R01AG062515-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10169220. Licensed CC0.

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