Time-Efficient Inspiratory Muscle Strength Training Lowers Blood Pressure and Improves Endothelial Function, NO Bioavailability, and Oxidative Stress in Midlife/Older Adults With Above-Normal Blood Pressure

Abstract

Background High-resistance inspiratory muscle strength training (IMST) is a novel, time-efficient physical training modality. Methods and Results We performed a double-blind, randomized, sham-controlled trial to investigate whether 6 weeks of IMST (30 breaths/day, 6 days/week) improves blood pressure, endothelial function, and arterial stiffness in midlife/older adults (aged 50-79 years) with systolic blood pressure ≥120 mm Hg, while also investigating potential mechanisms and long-lasting effects. Thirty-six participants completed high-resistance IMST (75% maximal inspiratory pressure, n=18) or low-resistance sham training (15% maximal inspiratory pressure, n=18). IMST was safe, well tolerated, and had excellent adherence (≈95% of training sessions completed). Casual systolic blood pressure decreased from 135±2 mm Hg to 126±3 mm Hg (P<0.01) with IMST, which was ≈75% sustained 6 weeks after IMST (P<0.01), whereas IMST modestly decreased casual diastolic blood pressure (79±2 mm Hg to 77±2 mm Hg, P=0.03); blood pressure was unaffected by sham training (all P>0.05). Twenty-four hour systolic blood pressure was lower after IMST versus sham training (P=0.01). Brachial artery flow-mediated dilation improved ≈45% with IMST (P<0.01) but was unchanged with sham training (P=0.73). Human umbilical vein endothelial cells cultured with subject serum sampled after versus before IMST exhibited increased NO bioavailability, greater endothelial NO synthase activation, and lower reactive oxygen species bioactivity (P<0.05). IMST decreased C-reactive protein (P=0.05) and altered select circulating metabolites (targeted plasma metabolomics) associated with cardiovascular function. Neither IMST nor sham training influenced arterial stiffness (P>0.05). Conclusions High-resistance IMST is a safe, highly adherable lifestyle intervention for improving blood pressure and endothelial function in midlife/older adults with above-normal initial systolic blood pressure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03266510.

Keywords: NO; exercise training; flow‐mediated dilation; hypertension; oxidative stress; reactive oxygen species.

Figure 1. Participant progress through the study.

IMST indicates inspiratory muscle strength training.

Figure 2. Casual systolic blood pressure (SBP) (A) and diastolic BP (DBP) (B) at baseline and after 6 weeks of inspiratory muscle strength training (IMST) or sham training.

Data are mean±SEM. *P<0.05 vs baseline.

Figure 3. Casual systolic blood pressure (SBP) (A) and diastolic BP (DBP) (B) at baseline, after 6 weeks of inspiratory muscle strength training (IMST) or sham training and after 6 weeks of abstaining from training (follow‐up).

n=15 IMST, n=14 sham. Data are mean±SEM. *P<0.05 vs baseline.

Figure 4. Brachial artery flow‐mediated dilation (FMD_BA) expressed as percent dilation in all subjects as average (A) and individual data (B), midlife/older men (n=9 inspiratory muscle strength training [IMST], n=10 sham) (C), and estrogen‐deficient postmenopausal (PM_E‐) women (n=7 IMST, n=8 sham) (D) at baseline and after 6 weeks of IMST or sham training.

Data are mean±SEM. *P<0.05 vs baseline. ^† P<0.05 vs sham.

Figure 5. Human umbilical vein endothelial cell NO production (A), phosphorylated endothelial NO synthase (p‐eNOS^ser1177) abundance (B), and reactive oxygen species (ROS) activity (C), following a 24‐hour incubation with serum from subjects, with example fluorescent images below ROS activity and NO production.

Data are mean±SEM. *P<0.05 vs baseline. ^† P<0.05 vs sham. IMST indicates inspiratory muscle strength training.