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

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $412,500

## Abstract

ABSTRACT
The prevalence of hypertension, increases with age from 30% of U.S. adults aged 20-44 to >75% 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. 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. This supplement contains the new NOT-AG-20-008 Specific Aim 4: Age-
dependent increases in blood pressure evoke blood brain barrier dysfunction and memory impairment
in the Sprague Dawley rat model of normal aging and in the TgF344-AD rat model of Alzheimer's
disease. This New Aim will address the novel hypothesis that age-dependent increases in BP evoke BBB
dysfunction and cognitive impairment in the SD rat model of normal aging and in the novel rat model of
Alzheimer's disease (TgF344-AD). The unique multi-disciplinary nature of our team, which combines expertise
in aging, hypertension, neuroscience, will utilize novel rat models of normal aging and AD and cutting edge in
vivo electrophysiology technology to comprehensively test our hypothesis. Completion of this New Aim, which
will directly address weaknesses in prior research in this area, will drive a new area research in the critical area
of vascular cognitive impairment and AD to support future planned R01 submissions.

## Key facts

- **NIH application ID:** 10131484
- **Project number:** 3R01AG062515-02S1
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Richard David Wainford
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,500
- **Award type:** 3
- **Project period:** 2019-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131484

## Citation

> US National Institutes of Health, RePORTER application 10131484, Aging and hypertension: Integrated renal and sympathetic control of blood pressure (3R01AG062515-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10131484. Licensed CC0.

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