Summary
Higher developed organisms are equipped with many central and local control mechanisms, which enable an adequate blood and oxygen supply to tissues over a wide range of demands. Global adaptive responses include changes in the circulatory and ventilatory system as well as increases in the oxygen carrying capacity of the blood. At the level of the specialized organs there exist additional control systems for the regulation of local blood flow. Most systems make use of highly specialized cells which are able to sense the oxygen partial pressure of the transport medium, blood, and within the tissues. In the past years, it has been shown that the vascular endothelium lining the entire circulatory system can actively modulate the vascular tone and platelet functions by the release of autacoids, among them prostacyclin and endothelium-derived nitric oxide (EDRF). Recent experiments demonstrate that the release of EDRF is\(P_{O_2 } \)-dependent, which suggests that endothelial cells may act as functional local oxygen sensors within the vascular system.
Similar content being viewed by others
References
Aw, T. Y., and Jones, D. P., ATP concentration gradients in cytosol of liver cells during hypoxia. Am. J. Physiol.249 (1985) C385–C392.
Bassenge, E., and Busse, R., Endothelial modulation of coronary tone. Prog. Cardiovasc. Dis.30 (1988) 349–380.
Bauer, C., and Kurtz, A., Oxygen sensing in the kidney and its relation to erythropoietin production. A. Rev. Physiol.51 (1989) 845–856.
Berne, R. M., and Rubio, R., Circulatory effects of tissue oxygen tension sensors, in: Tissue Hypoxia and Ischemia, pp. 163–174. Eds M. Reivich, R. Coburn, S. Lahiri and B. Chance. Plenum Press, New York-London 1977.
Bevilacqua, M. P., and Gimbrone, M. A. Jr, Inducible endothelial functions in inflammation and coagulation. Semin. Thromb. Hemost.13 (1987) 425–433.
Borda, L. J., Shuchleib, R., and Henry, P. D., Hypoxic contraction of isolated canine coronary artery. Mediation by potassium-dependent exocytosis of norepinephrine. Circ. Res.46 (1980) 870–879.
Busse, R., Förstermann, U., Matsuda, H., and Pohl, U., The role of prostaglandins in the endothelium-mediated vasodilatory response to hypoxia. Pflügers Arch.401 (1984) 77–83.
Busse, R., Trogisch, G., and Bassenge, E., The role of endothelium in the control of vascular tone. Basic Res. Cardiol.80 (1985) 475–490.
Busse, R., Ogilvie, A., and Pohl, U., Vasomotor activity of diadenosine triphosphate and diadenosine tetraphosphate in isolated arteries. Am. J. Physiol.254 (1988) H828–H832.
Busse, R., and Mülsch, A., Calcium-dependent nitric oxide synthesis in endothelial cytosol is mediated by calmodulin. FEBS Lett.265 (1990) 133–136.
Coburn, R. F., Grubb, B., and Aronson, R. D., Effect on cyanide on oxygen tension-dependent mechanical tension in rabbit aorta. Circ. Res.44 (1979) 368–378.
Detar, R., Mechanism of physiological hypoxia-induced depression of vascular smooth muscle contraction. Am. J. Physiol.238 (1980) H761–H769.
DiCorleto, P. E., Cultured endothelial cells produce multiple growth factors for connective tissue cells. Exp. Cell Res.153 (1984) 167–172.
Duling, B. R., and Berne, R. M., Longitudinal gradients in periarteriolar oxygen tension. A possible mechanism for the participation of oxygen in local regulation of blood flow. Circ. Res.27 (1970) 669–678.
Eyzaguirre, C., and Fidone, S. J., Transduction mechanisms in carotid body: glomus cells, putative neurotransmitters, and nerve endings. Am. J. Physiol.239 (1980) C135–C152.
Förstermann, U., Hertting, G., and Neufang, B., The importance of endogenous prostaglandins other than prostacyclin for the modulation of contractility of some rabbit blood vessels. Br. J. Pharmac.81 (1984) 623–630.
Furchgott, R. F., Role of endothelium in responses of vascular smooth muscle. Circ. Res.53 (1983) 557–573.
Grote, J., Siegel, G., Zimmer, K., and Adler, A., The influence of oxygen tension on membrane potential and tone of canine carotid artery smooth muscle. Adv. exp. Med. Biol.222 (1988) 481–487.
Harder, D. R., Sanchezferrer, C., Kauser, K., Stekiel, W. J., and Rubanyi, G. M., Pressure releases a transferable endothelial contractile factor in cat cerebral arteries. Circ. Res.65 (1989) 193–198.
Harlan, J. M., Consequences of leukocyte-vessel wall interactions in inflammatory and immune reactions. Semin. Thromb. Hemost.13 (1987) 434–444.
Hopwood, A. M., Lincoln, J., Kirkpatrick, K. A., and Burnstock, G., Adenosine 5′-triphosphate, adenosine and endothelium-derived relaxing factor in hypoxic vasodilatation of the heart. Eur. J. Pharmac.165 (1989) 323–326.
Jackson, W. F., and Duling, B. R., The oxygen sensitivity of hamster cheek pouch arterioles. In vitro and in situ studies. Circ. Res.53 (1983) 515–525.
Jackson, W. F., Prostaglandins do not mediate arteriolar oxygen reactivity. Am. J. Physiol.250 (1986) H1102–H1108.
Jackson, W. F., Lipoxygenase inhibitors block O2 responses in hamster cheek pouch arterioles. Am. J. Physiol.255 (1988) H711–H716.
Lands, W. E. M., Sauter, J., and Stone, G. W., Oxygen requirement for prostaglandin biosynthesis. Prostaglandins Med.1 (1978) 117–120.
Longhurst, J., and Zelis, R., Cardiovascular responses to local hindlimb hypoxemia: relation to the exercise reflex. Am. J. Physiol.237 (1979) H359–H365.
Lückhoff, A., Busse, R., Winter, I., and Bassenge, E., Characterization of vascular relaxant factor released from cultured endothelial cells. Hypertension9 (1987) 295–303.
Lückhoff, A., Pohl, U., and Busse, R., Increased free calcium in endothelial cells in response to hypoxia and restitution of normoxia. Pflügers Arch.406, Suppl. 1 (1986) R46.
Lund, N., Jorfeldt, L., and Lewis, D. H., Skeletal muscle oxygen pressure fields in healthy human volunteers. A study of the normal state and the effects of different arterial oxygen pressures. Acta anaesth. scand.24 (1980) 272–278.
Martin, W., Villani, G. M., Jothianandan, D., and Furchgott, R. F., Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J. Pharmac. exp. Ther.232 (1985) 708–716.
Moncada, S., and Vane, J. R., Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2 and prostacyclin. Pharmac. Rev.30 (1979) 293–331.
Mülsch, A., Böhme, E., and Busse, R., Stimulation of soluble guanylate cyclase by endothelium-derived relaxing factor from cultured endothelial cells. Eur. J. Pharmac.135 (1987) 247–250.
Mülsch, A., and Busse, R., NG-nitro-L-arginine (N5-[imino(nitroamino)methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis from L-arginine. Naunyn-Schmiedebergs Arch. Pharmak. (1989) in press.
Palmer, R. M. J., Ferrige, A. G., and Moncada, S., Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature327 (1987) 524–526.
Palmer, R. M. J., Ashton, D. S., and Moncada, S., Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature333 (1988) 664–666.
Pearson, J. D., Carleton, J. S., and Gordon, J. L., Metabolism of adenine nucleotides by ectoenzymes of vascular endothelial and smooth muscle cells in culture. Biochem. J.190 (1980) 421–429.
Pohl, U., Busse, R., and Kessler, M., Vascular resistance and tissue\(P_{O_2 } \) in skeletal muscle during perfusion with hypoxic blood, in: Cardiovascular System Dynamics, pp. 521–530. Eds T. Kenner, R. Busse and H. Hinghofer-Szalkay, Plenum Press, New York-London 1982.
Pohl, U., and Busse, R., Reduced nutritional blood flow in autoperfused rabbit hindlimbs following inhibition of endothelial vasomotor function, in: Resistance Arteries, pp. 10–16. Eds W. Halpern, B. Pegram, J. Brayden, K. Mackey, M. McLaughlin and G. Osol. Perinatology Press, Ithaca, New York 1988.
Pohl, U., and Busse, R., Hypoxia stimulates the release of endothelium-derived relaxant factor (EDRF). Am. J. Physiol.256 (1989) H1595–H1600.
Pohl, U., Galla, T., and Meßmer, K., Evidence for a role of EDRF in the hamster skin microcirculation: inhibitory effects of L-nitroarginine (abstract). Int. J. Microcirc.8 (1989).
Rees, D. D., Palmer, R. M., and Moncada, S., Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc. natl Acad. Sci. USA86 (1989) 3375–3378.
Rubanyi, G. M., and Vanhoutte, P. M., Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium. J. Physiol.364 (1985) 45–56.
Rubanyi, G. M., and Vanhoutte, P. M., Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. Am. J. Physiol.250 (1986) H822–H827.
Stern, D. M., Carpenter, B., and Nawroth, P. P., Endothelium and the regulation of coagulation. Path. Immun.5 (1986) 29–36.
Whatley, R. E., Zimmerman, G. A., McIntyre, T. M., Taylor, R., and Prescott, S. M., Production of platelet-activating factor by endothelial cells. Semin. Thromb. Hemost.13 (1987) 445–453.
Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y., Kobayashi, M., Mitsui, Y., Yazaki, Y., Goto, K., and Masak, T., A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature332 (1988) 411–415.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pohl, U. Endothelial cells as part of a vascular oxygen-sensing system: Hypoxia-induced release of autacoids. Experientia 46, 1175–1179 (1990). https://doi.org/10.1007/BF01936931
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01936931