Shear Stress, Myogenic Response, and Blood Flow Autoregulation

  • Yuansheng Gao


The vascular activity is tonically regulated by two major hemodynamic variations: a force parallel to the vessel wall generated by blood flow brushing against the endothelial layer termed as shear stress and a force perpendicular to the vessel wall resulted from blood pressure termed as tensile stress. Shear stress is sensed by various types of ion channels and membrane receptors as well as adhesion proteins, glycocalyx, and primary cilia on the cell surface. The acute activation of these mechanosensory receptors leads to altered vascular activity, while chronic change in shear stress results in adaptive structural remodeling of the blood vessels. An increase in blood pressure causes increased stretch of vascular smooth muscle cells (VSMCs) and vasoconstriction, while a decrease in blood pressure causes vasodilatation. This phenomenon is known as myogenic response. Vascular myogenic response is initiated by the opening of mechanosensitive ion channels such as TRPC6 channel, TRPM4 channel, and probably a heteromultimeric channel complex formed by the β and γ subunits of epithelial sodium channels and the subunit 2 of acid-sensing ion channel. Myogenic response is of fundamental importance for providing organ a relatively stable blood flow when exposed to changes in blood pressure, a phenomenon named as blood flow autoregulation. In renal circulation the autoregulation is achieved largely by the myogenic response and the macula densa–tubuloglomerular feedback response.


Shear stress Myogenic response Mechanoreceptor Blood flow autoregulation Renal 


  1. Ando J, Yamamoto K (2013) Flow detection and calcium signalling in vascular endothelial cells. Cardiovasc Res 99:260–268CrossRefPubMedGoogle Scholar
  2. Baeyens N, Bandyopadhyay C, Coon BG, Yun S, Schwartz MA (2016) Endothelial fluid shear stress sensing in vascular health and disease. J Clin Invest 126:821–828CrossRefPubMedPubMedCentralGoogle Scholar
  3. Baeyens N, Nicoli S, Coon BG, Ross TD, Van den Dries K, Han J, Lauridsen HM, Mejean CO, Eichmann A, Thomas JL, Humphrey JD, Schwartz MA (2015) Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point. Elife 4:e04645CrossRefPubMedCentralGoogle Scholar
  4. Bayliss WM (1902) On the local reactions of the arterial wall to changes of internal pressure. J Physiol 28:220–231CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bell PD, Lapointe JY, Peti-Peterdi J (2003) Macula densa cell signaling. Annu Rev Physiol 65:481–500CrossRefPubMedGoogle Scholar
  6. Boscardin E, Alijevic O, Hummler E, Frateschi S, Kellenberger S (2016) The function and regulation of acid-sensing ion channels (ASICs) and the epithelial Na+channel (ENaC): IUPHAR review 19. Br J Pharmacol 173(18):2671–2701CrossRefPubMedGoogle Scholar
  7. Burke M, Pabbidi MR, Farley J, Roman RJ (2014) Molecular mechanisms of renal blood flow autoregulation. Curr Vasc Pharmacol 12:845–858CrossRefPubMedPubMedCentralGoogle Scholar
  8. Busse R, Fleming I (2006) Vascular endothelium and blood flow. Handb Exp Pharmacol 176:43–78CrossRefGoogle Scholar
  9. Carlström M, Wilcox CS, Arendshorst WJ (2015) Renal autoregulation in health and disease. Physiol Rev 95:405–511CrossRefPubMedPubMedCentralGoogle Scholar
  10. Chiu JJ, Chien S (2011) Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev 91:327–387CrossRefPubMedGoogle Scholar
  11. Davies PF (2009) Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology. Nat Clin Pract Cardiovasc Med 6:16–26CrossRefPubMedGoogle Scholar
  12. Davies PF, Spaan JA, Krams R (2005) Shear stress biology of the endothelium. Ann Biomed Eng 33:1714–1718CrossRefPubMedGoogle Scholar
  13. Drummond HA (2015) Nontubular epithelial Na+ channel proteins in cardiovascular regulation. Physiol Rep 3.pii:e12404Google Scholar
  14. Drummond HA, Jernigan NL, Grifoni SC (2008) Sensing tension: epithelial sodium channel/acid-sensing ion channel proteins in cardiovascular homeostasis. Hypertension 51:1265–1271CrossRefPubMedPubMedCentralGoogle Scholar
  15. Earley S, Brayden JE (2015) Transient receptor potential channels in the vasculature. Physiol Rev 95:645–690CrossRefPubMedPubMedCentralGoogle Scholar
  16. Earley S, Waldron BJ, Brayden JE (2004) Critical role for transient receptor potential channel TRPM4 in myogenic constriction of cerebral arteries. Circ Res 95:922–929CrossRefPubMedGoogle Scholar
  17. Gannon KP, McKey SE, Stec DE, Drummond HA (2015) Altered myogenic vasoconstriction and regulation of whole kidney blood flow in the ASIC2 knockout mouse. Am J Physiol Renal Physiol 308:F339–F348CrossRefPubMedGoogle Scholar
  18. Ge Y, Gannon K, Gousset M, Liu R, Murphey B, Drummond HA (2012) Impaired myogenic constriction of the renal afferent arteriole in a mouse model of reduced βENaC expression. Am J Physiol Renal Physiol 302:F1486–F1493CrossRefPubMedPubMedCentralGoogle Scholar
  19. Greve JM, Les AS, Tang BT, Draney Blomme MT, Wilson NM, Dalman RL, Pelc NJ, Taylor CA (2006) Allometric scaling of wall shear stress from mice to humans: quantification using cine phase-contrast MRI and computational fluid dynamics. Am J Physiol Heart Circ Physiol 291:H1700–H1708CrossRefPubMedGoogle Scholar
  20. Guan Z, Pollock JS, Cook AK, Hobbs JL, Inscho EW (2009) Effect of epithelial sodium channel blockade on the myogenic response of rat juxtamedullary afferent arterioles. Hypertension 54:1062–1069CrossRefPubMedPubMedCentralGoogle Scholar
  21. Hall JE (2015) Guyton and Hall textbook of medical physiology, 13th edn. Elservier, PhiladelphiaGoogle Scholar
  22. Hill MA, Meininger GA (2012) Arteriolar vascular smooth muscle cells: mechanotransducers in a complex environment. Int J Biochem Cell Biol 44:1505–1510CrossRefPubMedPubMedCentralGoogle Scholar
  23. Hill-Eubanks DC, Gonzales AL, Sonkusare SK, Nelson MT (2014) Vascular TRP channels: performing under pressure and going with the flow. Physiology (Bethesda) 29:343–360Google Scholar
  24. Holtz J, Förstermann U, Pohl U, Giesler M, Bassenge E (1984) Flow-dependent, endothelium-mediated dilation of epicardial coronary arteries in conscious dogs: effects of cyclooxygenase inhibition. J Cardiovasc Pharmacol 6:1161–1169CrossRefPubMedGoogle Scholar
  25. Jernigan NL, Drummond HA (2005) Vascular ENaC proteins are required for renal myogenic constriction. Am J Physiol Renal Physiol 289:F891–F901CrossRefPubMedGoogle Scholar
  26. Jernigan NL, Drummond HA (2006) Myogenic vasoconstriction in mouse renal interlobar arteries: role of endogenous β and γENaC. Am J Physiol Renal Physiol 291:F1184–F1191CrossRefPubMedGoogle Scholar
  27. Kauffenstein G, Laher I, Matrougui K, Guérineau NC, Henrion D (2012) Emerging role of G protein-coupled receptors in microvascular myogenic tone. Cardiovasc Res 95:223–232CrossRefPubMedPubMedCentralGoogle Scholar
  28. Kellenberger S, Schild L (2015) International Union of Basic and Clinical Pharmacology. XCI. Structure, function, and pharmacology of acid-sensing ion channels and the epithelial Na+ channel. Pharmacol Rev 67:1–35CrossRefPubMedGoogle Scholar
  29. Kim EC, Choi SK, Lim M, Yeon SI, Lee YH (2013) Role of endogenous ENaC and TRP channels in the myogenic response of rat posterior cerebral arteries. PLoS One 8:e84194CrossRefPubMedPubMedCentralGoogle Scholar
  30. Li Y, Baylie RL, Tavares MJ, Brayden JE (2014) TRPM4 channels couple purinergic receptor mechanoactivation and myogenic tone development in cerebral parenchymal arterioles. J Cereb Blood Flow Metab 34:1706–1714CrossRefPubMedPubMedCentralGoogle Scholar
  31. Li Y, Brayden JE (2017) Rho kinase activity governs arteriolar myogenic depolarization. J Cereb Blood Flow Metab 37:140–152CrossRefPubMedGoogle Scholar
  32. Liu C, Montell C (2015) Forcing open TRP channels: mechanical gating as a unifying activation mechanism. Biochem Biophys Res Commun 460:22–25CrossRefPubMedPubMedCentralGoogle Scholar
  33. Loufrani L, Retailleau K, Bocquet A, Dumont O, Danker K, Louis H, Lacolley P, Henrion D (2008) Key role of α1β1-integrin in the activation of PI3-kinase-Akt by flow (shear stress) in resistance arteries. Am J Physiol Heart Circ Physiol 294:H1906–H1913CrossRefPubMedGoogle Scholar
  34. Papaioannou TG, Stefanadis C (2005) Vascular wall shear stress: basic principles and methods. Hell J Cardiol 46:9–15Google Scholar
  35. Rubanyi GM, Romero JC, Vanhoutte PM (1986) Flow-induced release of endothelium-derived relaxing factor. Am J Phys 250:H1145–H1149Google Scholar
  36. Schnermann J (2015) Concurrent activation of multiple vasoactive signaling pathways in vasoconstriction caused by tubuloglomerular feedback: a quantitative assessment. Annu Rev Physiol 77:301–322CrossRefPubMedGoogle Scholar
  37. Schnermann J, Briggs JP (2008) Tubuloglomerular feedback: mechanistic insights from gene-manipulated mice. Kidney Int 74:418–426CrossRefPubMedPubMedCentralGoogle Scholar
  38. Spassova MA, Hewavitharana T, Xu W, Soboloff J, Gill DL (2006) A common mechanism underlies stretch activation and receptor activation of TRPC6 channels. Proc Natl Acad Sci U S A 103:16586–16591CrossRefPubMedPubMedCentralGoogle Scholar
  39. Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA (2005) A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437:426–431CrossRefPubMedGoogle Scholar
  40. Welsh DG, Morielli AD, Nelson MT, Brayden JE (2002) Transient receptor potential channels regulate myogenic tone of resistance arteries. Circ Res 90:248–250CrossRefPubMedGoogle Scholar
  41. Ye GJ, Nesmith AP, Parker KK (2014) The role of mechanotransduction on vascular smooth muscle myocytes’ [corrected] cytoskeleton and contractile function. Anat Rec (Hoboken) 297:1758–1769CrossRefGoogle Scholar
  42. Yue Z, Xie J, Yu AS, Stock J, Du J, Yue L (2015) Role of TRP channels in the cardiovascular system. Am J Physiol Heart Circ Physiol 308:H157–H182CrossRefPubMedGoogle Scholar
  43. Zhou J, Li YS, Chien S (2014) Shear stress-initiated signaling and its regulation of endothelial function. Arterioscler Thromb Vasc Biol 34:2191–2198CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Yuansheng Gao
    • 1
  1. 1.Department of Physiology and PathophysiologyPeking University Health Science CenterBeijingChina

Personalised recommendations