# Inspiratory muscle strength training for lowering systolic blood pressure in midlife and older adults with chronic kidney disease

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $535,533

## Abstract

PROJECT SUMMARY
Chronic kidney disease (CKD) is a major public health concern that has reached epidemic proportions.
Hypertension is a leading modifiable risk factor for cardiovascular disease (CVD) and end-stage kidney
disease, yet 50-70% of adults with CKD fail to achieve blood pressure (BP) control to <130/80 mmHg. A key
process linking high systolic BP (SBP) to CVD is vascular endothelial dysfunction, mediated by excessive
reactive oxygen species (ROS)-induced oxidative stress and reductions in nitric oxide (NO) bioavailability. NO
is also critical in the regulation of renal blood flow (RBF), which is intimately related to BP and vascular
function. Guidelines recommend a stepwise combination of lifestyle modifications and drug therapy to lower
BP, yet adherence to lifestyle modifications such as aerobic exercise is poor in patients with CKD. Drug
regimens often involve multiple medications, as hypertension is challenging to control in CKD. High-resistance
inspiratory muscle strength training (IMST) is a novel lifestyle intervention involving repeated inhalations
against a resistive load using a hand-held device. In a randomized, double-blind, sham controlled, parallel
group design, R21-funded pilot study in 36 midlife/older men and women with baseline SBP ≥120 mmHg, we
showed that IMST (30 breaths [5 minutes]/day at 75% of maximal inspiratory pressure, 6 days [30
minutes]/week for 6 weeks) had excellent adherence (95% of prescribed sessions completed) and lowered
casual (resting) SBP by 9±2 mmHg. IMST improved endothelial function (brachial artery flow-mediated
dilation, FMDBA) by 40%, linked to increased endothelial NO synthase (eNOS) activation and NO
bioavailability, reduced ROS production and oxidative stress, and changes in circulating factors. Importantly,
the effects of IMST on SBP and FMDBA were even greater in individuals with an estimated glomerular filtration
rate (eGFR) <75 mL/min/1.73m2. To establish the efficacy of high-resistance IMST in midlife/older adults (≥50
years) with moderate-to-severe CKD (eGFR 20-59 mL/min/1.73m2) and inadequately controlled hypertension
(SBP 130-159 mm Hg), we propose a randomized, parallel group, sham-controlled, double-blind, clinical trial to
evaluate the effects of a clinically relevant treatment duration of IMST (3 months) on SBP, FMDBA, NO
bioavailability, eNOS activation, ROS/oxidative stress, circulating factors, and RBF.
Aim 1: To measure casual SBP (primary outcome) and 24-hour (ambulatory) SBP (secondary outcome)
before (baseline) and after 3 months of IMST or Sham training.
Aim 2: To measure FMDBA (secondary outcome) before and after IMST or Sham training.
Aim 3: To determine: a) endothelial cell culture eNOS, NO and ROS production pre-post IMST or Sham serum
exposure; b) markers of oxidative stress and antioxidant status in biopsied endothelial cells; c) the identity of
the plasma metabolites involved; d) RBF by functional magnetic resonance imaging.
Aim 4: To assess adherence (completed...

## Key facts

- **NIH application ID:** 10906258
- **Project number:** 5R01DK130266-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Michel Benjamin Chonchol
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $535,533
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906258

## Citation

> US National Institutes of Health, RePORTER application 10906258, Inspiratory muscle strength training for lowering systolic blood pressure in midlife and older adults with chronic kidney disease (5R01DK130266-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10906258. Licensed CC0.

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