Translational Potential of High-Resistance Inspiratory Muscle Strength Training

Daniel H. Craighead; Kaitlin A. Freeberg; Grace S.Maurer; Valerie H. Myers; Douglas R. Seals


Exerc Sport Sci Rev. 2022;50(3):107-117. 

In This Article

Abstract and Introduction


Age-associated cardiovascular (CV) dysfunction increases the risk for CV diseases. Aerobic exercise training can improve CV function, but only a minority of adults meet aerobic exercise guidelines. High-resistance inspiratory muscle strength training is a time-efficient lifestyle intervention that may promote adherence and improve CV function. However, further investigation is needed to translate inspiratory muscle strength training into the public health domain.


Aging is the primary risk factor for cardiovascular diseases (CVD), the leading cause of death in developed and developing societies.[1] The number of older adults in the United States and other countries is expected to significantly increase in the coming years, leading to an increased burden of CVD.[2] The increased risk for CVD with aging is attributable, in large part, to age-related changes in CV function (Figure 1). Key changes in CV function with advancing age include increases in blood pressure (BP), primarily systolic BP (SBP) after age 50 yr, vascular endothelial dysfunction, and stiffening of the large elastic (carotid and aorta) arteries.[3] The primary mechanisms underlying these age-related changes in CV function are oxidative stress and chronic low-grade inflammation.[4–7]

Figure 1.

Conceptual model outlining the barriers for adhering to aerobic exercise and the potential characteristics of high-resistance inspiratory muscle strength training (IMST) that make it a promising intervention for public health implementation.

Oxidative stress is caused by excessive production of reactive oxygen species, particularly superoxide, in the face of an inadequate (or complete lack of) compensatory increase in antioxidant defenses, most importantly antioxidant enzyme abundance.[6,8] The excessive superoxide directly reacts with nitric oxide (NO), a key vasodilatory and atheroprotective molecule produced by the vascular endothelium,[5,8,9] to form peroxynitrite.[10] Thus, excess superoxide bioactivity leads to a reduction in NO bioavailability and an impairment in endothelial function. Excessive superoxide-induced oxidative stress also stimulates remodeling of the arterial extracellular matrix, causing fragmentation of elastin fibers with compensatory deposition of collagen and the formation of structural protein crosslinking molecules, such as advanced glycation end products.[3,11]

Inflammation involves a chronic, low-grade increase in proinflammatory cytokines, such as C-reactive protein (CRP) and interleukin-6.[12,13] A key mechanism contributing to chronic low-grade inflammation is the continuous activation of the proinflammatory transcription factor and master regulator of inflammation, nuclear factor κB.[5,6,14]

Collectively, the changes in oxidative stress and inflammation with aging induce increases in SBP, vascular endothelial dysfunction, and large elastic artery stiffening. Age-related changes in SBP, vascular function and the associated mechanisms can be mitigated by so-called first-line lifestyle strategies. Most prominent among these strategies is regular aerobic exercise training.[5,15] However, as discussed later, only a minority (<40%) of midlife and older adults (i.e., adults aged 50 yr and older) presently meet guidelines for aerobic exercise due to multiple barriers to adherence.[16,17] Therefore, there is a need for novel interventions that improve CV function with aging.

The purpose of this Perspective for Progress is to discuss the current knowledge and future research directions regarding high-resistance, low-repetition inspiratory muscle strength training (IMST), a novel, time-efficient form of physical activity that uses the respiratory muscles and may improve CV function with aging.[18,19] As it poses a minimal time burden, high-resistance IMST holds particular promise for translation into the public health domain and for use in rehabilitation settings. To provide context and contrast for future research on IMST, we will start by briefly discussing aerobic exercise, an established form of physical activity that has been the subject of intense investigation along the entirety of the basic science-to-public health research spectrum. We then will review available evidence on high-resistance IMST for improving CV function with aging, before highlighting the potential synergy between IMST and digital health technologies for accelerating the translation of IMST into the public health domain. We will conclude by providing our view on important future research directions on this novel lifestyle intervention.