# Sympathetic Regulation of Large Artery Stiffness in Humans with Age-Related Isolated Systolic Hypertension

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2022 · $343,913

## Abstract

Project Summary/Abstract
Stiffness of the large elastic central arteries (e.g., aorta and carotids) increases with advancing
age and is a robust predictor of incident cardiovascular disease (CVD) events among older
adults. The age-related increase in central artery stiffness is associated with a concomitant rise
in systolic blood pressure (BP) and pulse pressure (PP) and subsequently the development of
isolated systolic hypertension (ISH) in many older adults. Consequently, higher PP results in
greater pulsatile pressure and flow penetrating into high blood flow organs such as the brain
causing subclinical target organ damage. Sympathetic nerve activity (SNA) also increases with
advancing age and is associated with cardiovascular target organ damage including left
ventricular hypertrophy and intima-medial thickness (IMT) of peripheral conduit arteries, but it
remains unclear whether enhanced SNA modulates the age-related increase in central artery
stiffness and associated augmented carotid pressure and flow pulsatility and increased IMT.
Therefore, the objectives of this application are to 1) determine the contribution of SNA to the
age-related increase in aortic stiffness and reduced carotid compliance, and augmented carotid
pressure and flow pulsatility and IMT among older adults with ISH, and 2) determine the
effectiveness of chronic inhibition of SNA for reducing large artery stiffness, carotid pressure
and flow pulsatility and IMT among older adults with ISH. In Aim 1, we will enroll 30 older (age
60-85 years) adults (50% women/50% men) with untreated stage 1 or stage 2 ISH (systolic BP
130-159 mmHg; diastolic BP <90mmHg) in a repeated measures experimental study assessing
aortic stiffness (carotid-femoral pulse wave velocity, PWV) and carotid artery compliance and
pressure pulsatility index at baseline and during -15 and -30 mmHg of lower body negative
pressure. We hypothesize that acute experimental elevations in SNA will result in transient
increases in carotid-femoral PWV and decreases in carotid compliance resulting in higher
carotid pressure and flow pulsatility. In Aim 2, we will enroll 78 healthy older men and women
(age 60-85 years) with untreated or treated ISH in a randomized, placebo-controlled double
blind study. We hypothesize that 4 weeks of chronic SNA inhibition with oral clonidine will result
in clinically meaningful decreases in aortic stiffness and increases in carotid artery compliance,
causing significant reductions in carotid pressure and flow pulsatility index and IMT. The
proposed research will fundamentally advance our understanding of the regulation of large
elastic artery stiffness by SNA among older humans with ISH, and provide valuable insight into
SNA as a novel therapeutic target among older adults with ISH for lowering CVD risk.

## Key facts

- **NIH application ID:** 10400014
- **Project number:** 5R01AG063790-03
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Gary L. Pierce
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $343,913
- **Award type:** 5
- **Project period:** 2020-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400014

## Citation

> US National Institutes of Health, RePORTER application 10400014, Sympathetic Regulation of Large Artery Stiffness in Humans with Age-Related Isolated Systolic Hypertension (5R01AG063790-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10400014. Licensed CC0.

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