European Journal of Applied Physiology

, Volume 114, Issue 3, pp 531–544

Blood pressure regulation VIII: resistance vessel tone and implications for a pro-atherogenic conduit artery endothelial cell phenotype

  • Jaume Padilla
  • Nathan T. Jenkins
  • M. Harold Laughlin
  • Paul J. Fadel
Invited Review


Dysfunction of the endothelium is proposed as the primary initiator of atherosclerotic peripheral artery disease, which occurs mainly in medium- to large-sized conduit arteries of the lower extremities (e.g., iliac, femoral, popliteal arteries). In this review article, we propose the novel concept that conduit artery endothelial cell phenotype is determined, in part, by microvascular tone in skeletal muscle resistance arteries through both changes in arterial blood pressure as well as upstream conduit artery shear stress patterns. First, we summarize the literature supporting the involvement of sympathetic nerve activity (SNA) and nitric oxide (NO) in the modulation of microvascular tone and arterial blood pressure. We then focus on the role of elevated blood pressure and shear stress profiles in modulating conduit artery endothelial cell phenotype. Last, we discuss findings from classic and emerging studies indicating that increased vascular resistance, as it occurs in the context of increased SNA and/or reduced NO bioavailability, is associated with greater oscillatory shear stress (e.g., increased retrograde shear) in upstream conduit arteries. The ideas put forth in this review set the stage for a new paradigm concerning the mechanistic link between increased microvascular tone and development of conduit artery endothelial dysfunction and thus increased risk for peripheral artery disease. Indeed, a vast amount of evidence supports the notion that excessive blood pressure and oscillatory shear stress are potent pro-atherogenic signals to the endothelium.


Sympathetic nerve activity Nitric oxide Shear stress Blood pressure Endothelial function Atherosclerosis 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Jaume Padilla
    • 1
  • Nathan T. Jenkins
    • 1
  • M. Harold Laughlin
    • 1
    • 2
    • 3
  • Paul J. Fadel
    • 2
    • 3
  1. 1.Biomedical SciencesUniversity of MissouriColumbiaUSA
  2. 2.Medical Pharmacology and PhysiologyUniversity of MissouriColumbiaUSA
  3. 3.Dalton Cardiovascular Research CenterUniversity of MissouriColumbiaUSA

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