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Principal Investigator: E. FIONA BAILEY
Organization: UNIVERSITY OF ARIZONA
Fiscal Year: 2024
Award: $669,435
Funding agency: National Institute on Aging
Project Summary
Exercise has well-documented benefits for systolic blood pressure (SBP) and cardiovascular health. Whereas
current guidelines advocate ~150 min moderate intensity exercise/week, our preliminary data show ~5
min/day of inspiratory muscle strength training (IMST) for 6 weeks lowers casual (resting) SBP by ~12 mmHg.
This simple approach to lowering BP could be applied to almost any population however we propose to
study IMST in older adults with obstructive sleep apnea (OSA). OSA is an ideal population to target because
OSA prevalence is growing and because snoring and apneas result in chronic intermittent hypoxemia that
drives sympathetic nervous system (SNS) hyperactivity, endothelial dysfunction and hypertension. These
substantive risks for cardiovascular disease are compounded by poor adherence to the mainstay treatment
continuous positive airway pressure (<50%), obesity, fatigue and a robust intolerance for exercise.
Our findings in healthy young adults (n=50) show IMST-related reductions in BP are mediated by
decreases in systemic vascular resistance, suggesting changes in vascular tone and function. Consistent with
this hypothesis, our results from a pilot clinical trial in adults with OSA (n=24) show IMST-related reductions in
plasma norepinephrine levels (PNE) and muscle sympathetic nerve activity (MSNA), both markers of SNS
activity. Our preliminary mechanistic assessments indicate IMST may lower circulating concentrations of other
vasoconstrictor factors and increase nitric oxide (NO)-mediated endothelium-dependent dilation. And, findings
in a novel endothelial cell culture model, point to increases in NO and declines in reactive oxygen species
(ROS) and oxidative stress. However, it is unknown if: 1) IMST lowers casual and 24-h (ambulatory) SBP in
older adults with OSA; 2) the reductions in SBP are long-lasting; 3) arterial stiffness, NO-mediated endothelial
dilation and/or oxidative stress are improved; and 4) if adherence in this population is high long term.
We propose a randomized, double-blind, placebo-controlled, clinical trial to establish the efficacy of IMST
(75% maximum inspiratory pressure, [PImax]) 5 days/week for 24 weeks vs. placebo (15%PImax) (n=61/group)
for lowering SBP in adults (>50 years) with above normal BP and OSA. We hypothesize that IMST will lower
SBP via reductions in SNS activity and circulating vasoconstrictor factors, improvements in vascular function,
and reductions in oxidative stress/inflammation and that reductions in SBP will be sustained after IMST.
Aim 1: To determine casual and 24-h ambulatory BP; before/after, and 4- and 12-weeks post-IMST/placebo
training. Safety, tolerability and adherence also will be assessed.
Aim 2: To measure arterial stiffness, brachial artery flow-mediated dilation (FMDBA), plasma PNE, MSNA,
vasoconstrictor factors and inflammation; before/after, and 4- and 12-weeks post-IMST/placebo training.
Aim 3: To evaluate superoxide related suppression of FMDBA, and markers of oxidative stress and antioxidant
defense in endothelial cells from subjects before/after, and 4- and 12-weeks post-IMST/placebo training.
Terms: <21+ years old><Active Oxygen><Acute><Adherence><Adult><Adult Human><Advocate><Aerobic Activity><Aerobic Exercise><Aerobic Training><Aerobic fitness><Antioxidants><Apnea><Ascorbic Acid><B cell differentiation factor><B cell stimulating factor 2><B-Cell Differentiation Factor><B-Cell Differentiation Factor-2><B-Cell Stimulatory Factor-2><BCDF><BP reduction><BSF-2><BSF2><Biopsy><Blood Plasma><Blood Pressure><Blood Serum><Blood Vessels><CPAP><CPAP Ventilation><CSIF><CSIF-10><Cardiac Chronotropism><Cardiac Output><Cell Communication and Signaling><Cell Culture Techniques><Cell Signaling><Chronic><Clinical Treatment><Clinical Trials><Continuous Positive Airway Pressure><Cytokine Synthesis Inhibitory Factor><Data><Development><Diastolic Pressure><Diastolic blood pressure><Disease><Disorder><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><Elasticity><Endogenous Nitrate Vasodilator><Endothelial Cells><Endothelium><Endothelium-Derived Nitric Oxide><Event><Exercise><Fatigue><Femur><Guidelines><HPGF><Health><Heart Rate><Hepatocyte-Stimulating Factor><Hour><Human><Hybridoma Growth Factor><Hyperactivity><Hypertension><Hypoxemia><IFN-beta 2><IFNB2><IL-10><IL-6><IL10><IL10A><IL6 Protein><Inflammation><Inflammatory><Infusion><Infusion procedures><Interleukin 10 Precursor><Interleukin-10><Interleukin-6><Intervention><Intervention Strategies><Intracellular Communication and Signaling><Lack of Energy><Levarterenol><Levonorepinephrine><MGI-2><Measures><Mediating><Methods><Modeling><Modern Man><Molecular><Mononitrogen Monoxide><Muscle><Muscle Tissue><Myeloid Differentiation-Inducing Protein><Nerve><Nitric Oxide><Nitrogen Monoxide><Nitrogen Protoxide><Noradrenaline><Norepinephrine><Obesity><Obstructive Sleep Apnea><Over weight><Overweight><Oxidative Stress><Oxygen Radicals><Patients><Peripheral Resistance><Physiologic pulse><Placebo Control><Placebos><Plasma><Plasma Serum><Plasmacytoma Growth Factor><Population><Prevalence><Preventative strategy><Prevention strategy><Preventive strategy><Pro-Oxidants><Production><Pulse><Randomized><Reactive Oxygen Species><Research><Rest><Reticuloendothelial System, Serum, Plasma><Safety><Serum><Sham Treatment><Signal Transduction><Signal Transduction Systems><Signaling><Sleep Apnea><Sleep Apnea Syndromes><Sleep Hypopnea><Sleep-Disordered Breathing><Snoring><Source><Superoxide Anion><Superoxide Radical><Superoxides><Sympathetic Nervous System><Syndrome, Sleep Apnea, Obstructive><Systemic Vascular Resistance><Time><Total Peripheral Resistance><Training><Umbilical vein><United States><VIT C><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Vasoactive Agonists><Vasoconstrictor Agents><Vasoconstrictor Drugs><Vasoconstrictors><Vasopressor Agents><Vitamin C><Woman><adiposity><adult youth><adulthood><airflow limitation><airflow obstruction><airway limitation><airway obstruction><arterial stiffening><arterial stiffness><artery stiffening><artery stiffness><biological signal transduction><blood pressure reduction><brachial artery><cardiovascular disease risk><cardiovascular disorder risk><cardiovascular health><cardiovascular risk><cardiovascular risk factor><cell culture><cell cultures><clinical relevance><clinical significance><clinically relevant><clinically significant><corpulence><determine efficacy><developmental><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><endothelial cell derived relaxing factor><endothelial dysfunction><evaluate efficacy><evidence base><examine efficacy><exercise intensity><exercise intolerance><heart output><high blood pressure><hyperpiesia><hyperpiesis><hypertension treatment><hypertensive disease><hypertensive disorder><hypoxemic><improved><in vivo><indexing><inflammation marker><inflammatory marker><infusions><insight><interferon beta 2><interventional strategy><lower BP><lower blood pressure><lowers blood pressure><men><molecular biomarker><molecular marker><muscle strength><muscle strengthening><muscular><novel><obstructed airflow><obstructed airway><older adult><older adulthood><peer><placebo controlled><preservation><pressure><randomisation><randomization><randomized placebo-controlled clinical trial><randomly assigned><reduce BP><reduce blood pressure><reduction in BP><reduction in blood pressure><respiratory airway obstruction><response><sedentary><sham therapy><sleep-related breathing disorder><strength training><tool><trial comparing><trial regimen><trial treatment><vascular><vasopressor><young adult><young adulthood>