Hypoxic pulmonary vasoconstriction (HPV), also known as the Euler-Liljestrand mechanism, is a
physiological phenomenon in which small
pulmonary arteries constrict in the presence of alveolar
hypoxia (low oxygen levels). By redirecting blood flow from poorly-ventilated lung regions to well-ventilated lung regions, HPV is thought to be the primary mechanism underlying
ventilation/perfusion matching.[1][2]
The process might initially seem counterintuitive, as low oxygen levels might theoretically stimulate increased blood flow to the lungs to increase gas exchange. However, the purpose of HPV is to distribute bloodflow regionally to increase the overall efficiency of gas exchange between air and blood. While the maintenance of
ventilation/perfusion ratio during regional obstruction of airflow is beneficial, HPV can be detrimental during global alveolar hypoxia which occurs with exposure to
high altitude, where HPV causes a significant increase in total
pulmonary vascular resistance, and pulmonary arterial pressure, potentially leading to
pulmonary hypertension and
pulmonary edema.
The classical explanation of HPV involves inhibition of hypoxia-sensitive
voltage-gated potassium channels in pulmonary artery smooth muscle cells leading to depolarization.[3][4] This depolarization activates
voltage-dependent calcium channels, which increases intracellular calcium and activates smooth muscle contractile machinery which in turn causes vasoconstriction. However, later studies have reported additional ion channels and mechanisms that contribute to HPV, such as
transient receptor potential canonical 6 (TRPC6) channels, and transient receptor potential vanilloid 4 (TRPV4) channels.[5][6] Recently it was proposed that hypoxia is sensed at the alveolar/capillary level, generating an electrical signal that is transduced to pulmonary arterioles through
gap junctions in the pulmonary
endothelium to cause HPV.[7] This contrasts with the classical explanation of HPV which presumes that hypoxia is sensed at the pulmonary artery smooth muscle cell itself. Specialized
epithelial cells (neuroepithelial bodies) that release serotonin have been suggested to contribute to hypoxic pulmonary venoconstriction.[8]
High-altitude mountaineering can induce pulmonary hypoxia due to decreased atmospheric pressure. This hypoxia causes vasoconstriction that ultimately leads to
high altitude pulmonary edema (HAPE). For this reason, some climbers carry supplemental oxygen to prevent hypoxia, edema, and HAPE. The standard drug treatment of
dexamethasone does not alter the hypoxia or the consequent vasoconstriction, but stimulates fluid reabsorption in the lungs to reverse the edema. Additionally, several studies on native populations remaining at high altitudes have demonstrated to varying degrees the blunting of the HPV response.[9]
References
^Silverthorn, D.U. (2016). "Chapter 14-15". Human physiology (7th ed.). New York: Pearson Education. p. 544.
^Post, J. M.; Hume, J. R.; Archer, S. L.; Weir, E. K. (1992-04-01). "Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction". The American Journal of Physiology. 262 (4 Pt 1): C882–890.
doi:
10.1152/ajpcell.1992.262.4.C882.
ISSN0002-9513.
PMID1566816.
^Yuan, X. J.; Goldman, W. F.; Tod, M. L.; Rubin, L. J.; Blaustein, M. P. (1993-02-01). "Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes". The American Journal of Physiology. 264 (2 Pt 1): L116–123.
doi:
10.1152/ajplung.1993.264.2.L116.
ISSN0002-9513.
PMID8447425.
S2CID31223667.
^Lauweryns, Joseph M.; Cokelaere, Marnix; Theunynck, Paul (1973). "Serotonin Producing Neuroepithelial Bodies in Rabbit Respiratory Mucosa". Science. 180 (4084): 410–413.
doi:
10.1126/science.180.4084.410.
ISSN0036-8075.
^Swenson, Erik R. (24 Jun 2013). "Hypoxic Pulmonary Vasoconstriction". High Altitude Medicine & Biology. 14 (2): 101–110.
doi:
10.1089/ham.2013.1010.
PMID23795729.
Von Euler US, Liljestrand G (1946). "Observations on the pulmonary arterial blood pressure in the cat". Acta Physiol. Scand. 12 (4): 301–320.
doi:
10.1111/j.1748-1716.1946.tb00389.x.
Völkel N, Duschek W, Kaukel E, Beier W, Siemssen S, Sill V (1975). "Histamine-an important mediator for the Euler-Liljestrand mechanism?". Pneumonologie. Pneumonology. 152 (1–3): 113–21.
doi:
10.1007/BF02101579.
PMID171630.
S2CID27167180.
Porcelli RJ, Viau A, Demeny M, Naftchi NE, Bergofsky EH (1977). "Relation between hypoxic pulmonary vasoconstriction, its humoral mediators and alpha-beta adrenergic receptors". Chest. 71 (2 suppl): 249–251.
doi:
10.1378/chest.71.2_Supplement.249.
PMID12924.