(In)activity-related neuroplasticity in brainstem control of sympathetic outflow: Unraveling underlying molecular, cellular, and anatomical mechanisms

Nicholas A. Mischel, Madhan Subramanian, Maryetta D. Dombrowski, Ida J. Llewellyn-Smith, Patrick J. Mueller

Research output: Contribution to journalReview articlepeer-review

25 Citations (Scopus)


More people die as a result of physical inactivity than any other preventable risk factor including smoking, high cholesterol, and obesity. Cardiovascular disease, the number one cause of death in the United States, tops the list of inactivity-related diseases. Nevertheless, the vast majority of Americans continue to make lifestyle choices that are creating a rapidly growing burden of epidemic size and impact on the United States healthcare system. It is imperative that we improve our understanding of the mechanisms by which physical inactivity increases the incidence of cardiovascular disease and how exercise can prevent or rescue the inactivity phenotype. The current review summarizes research on changes in the brain that contribute to inactivity-related cardiovascular disease. Specifically, we focus on changes in the rostral ventrolateral medulla (RVLM), a critical brain region for basal and reflex control of sympathetic activity. The RVLM is implicated in elevated sympathetic outflow associated with several cardiovascular diseases including hypertension and heart failure. We hypothesize that changes in the RVLM contribute to chronic cardiovascular disease related to physical inactivity. Data obtained from our translational rodent models of chronic, voluntary exercise and inactivity suggest that functional, anatomical, and molecular neuroplasticity enhances glutamatergic neurotransmission in the RVLM of sedentary animals. Collectively, the evidence presented here suggests that changes in the RVLM resulting from sedentary conditions are deleterious and contribute to cardiovascular diseases that have an increased prevalence in sedentary individuals. The mechanisms by which these changes occur over time and their impact are important areas for future study.

Original languageEnglish
Pages (from-to)H235-H243
Number of pages9
JournalAmerican Journal of Physiology-Heart and Circulatory Physiology
Issue number2
Publication statusPublished - 15 Jul 2015


  • Arterial pressure
  • Cardiovascular disease
  • Inactivity
  • Neurons
  • Sympathetic nervous system


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