Endothelial (intimal) mechanism of cerebral hemodynamics regulation: changing views

08 April 2011
Written by V.M. Chertok, A.E. Kotsyuba

  UDK: 611.018.74:612.82/.824:612.133 | Pages: 17-26 | Read full text  | Download PDF 


The literature overview describes modern standpoints about the role of vessel endothelium in regulating cerebral hemodynamics – from complete denial of this possibility to recognition of the leading role of endothelial mechanism in controlling vessel functions. The paper summarises results of authors’ researches and literature over the last fifty years into the endothelial (intimal) mechanism of blood circulation regulation. As reported, the adequate blood supply of brain results from interaction between several mechanisms. Researching these mechanisms will allow identify the role of endothelium in the single system of blood supply of brain.

Links to authors:

V.M. Chertok, A.E. Kotsyuba
Vladivostok State Medical University (2 Ostryakova Av. Vladivostok 690950 Russian Federation)

  1. Baramidze D.G., Mchedlishvili G.I. Operation of microvascular mechanisms in pial arteries, Fiziol. zhurn. SSSR. 1975. Vol. 61, No. 3. P.1493–1500.
  2. Gannushkina I.V., Lebedeva N.V. Hypertensive encephalopathy. M.: Medicina, 1987. 224 p.
  3. Kocjuba A.E., Chertok V.M. Nitroxide containing elements of sensory innervations in cerebral arteries, Pacific Medical Journal. 2009. No. 2. P. 69–72.
  4. Kocjuba A.E., Babich E.V., Chertok V.M. Vasomotor innervations of the human brain arteries soft shell with different diameters in hypertension, Zh. nevropatol. i psihiatrii. 2009. No. 9. P.56–62.
  5. Kocjuba A.E., Kocjuba E.P., Chertok V.M. The nitroxidergic nerves of intracerebral vessels, Morfologija. 2009. Vol. 135, No. 2. P. 27–32.
  6. Kocjuba A.E., Chertok V.M., Babich E.V. The nitroxidergic neurons of human bulbar vasomotor center in hypertension, Zhurn. nevropatol. i psihiatrii. 2010. No. 2. P 61–65.
  7. Melkumjanc A.M., Balashov S.A. The mechanosensitive of arterial endothelium. Tver: Triada, 2005. 208 p.
  8. Motavkin P.A. About spinal sensory innervation of the intraorgan brain blood vessels, Dokl. AN SSSR.1960. Vol. 133, No. 6. P. 1509–1511.
  9. Motavkin P.A. What and how innervated in the brain? Morfologija. 2007. No. 1. P. 82–84. 
  10. Motavkin P.A., Chertok V.M. The histophysiology of vascular mechanisms in cerebral circulation. M.: Medicina, 1980. 132 p. 
  11. Motavkin P.A., Chertok V.M. The ultrastructure of nerve arteries in brain base, Arhiv anat., gistol. i jembriol. 1979. Vol. 76, No. 1. P. 13–19.
  12. Motavkin P.A., Markina L.D., Bozhko G.G. The comparative morphology of cerebral blood flow vascular mechanisms in
    vertebrates. M.: Nauka, 1981. 206 p.
  13. Motavkin P.A., Chertok V.M., Pigolkin Ju.I. The morphological researches of cerebral blood flow regulatory mechanisms, Arh. anat., gistol. i jembriol. 1982. No. 6. P. 42–49.
  14. Motavkin P.A., Pigolkin Ju.I., Lomakin A.V., Chertok V.M. The receptor glomeruli and their ultrastructural organization in the arteries of the human pia mater, Arhiv anat., gistol. i jembriol. 1989. No. 9. P. 14–19.
  15. Motavkin P.A., Pigolkin Ju.I., Kaminskij Ju.V. The histophysiology circulation in the spinal cord. M.: Nauka. 1994. 232 p.
  16. Motavkin P.A., Chertok V.M. The brain innervation, Pacific Medical Journal. 2008. No. 3. P. 11–23.
  17. Mchedlishvili G.I. The function of the brain vascular mechanisms. Its role in the regulation and in the pathology of cerebral circulation. L.: Nauka, 1968. 200 p.
  18. Mchedlishvili G.I., Nikolajshvili L.S. The researches of the blood supply correlation physiological mechanisms and the functional state of the cerebral cortex, Fiziol. zhurn. SSSR. 1966. Vol. 52, No. 5. P. 380–386.
  19. Mchedlishvili G.I., Nikolajshvili L.S., Antija R.V. The researches of pial arteries response mechanisms in hyper‑and hypotension, Fiziol. zhurn. SSSR, 1976. Vol. 62, No. 3. P. 104–114.
  20. Smeshko V.N., Hajutin V.M. The sensitivity of the muscle‑type arteries to the blood flow, Fiziol. zhurn. SSSR. 1979. Vol. 65, No. 2. P. 291–298.
  21. Chertok V.M. The functional morphology of the base brain arteries: thesis. Vladivostok, 1977. 225 p.
  22. Chertok V.M., Pigolkin Ju.I., Motavkin P.A. Cholinergic and adrenergic innervation of the human intracerebral arteries in ontogeny, Arh. anat., gistol. i jembriol. 1983. Vol. 84, No. 2. P. 22–29.
  23. Chertok V.M., Pigolkin Ju.I., Miroshnichenko N.V. Histochemical characteristics of the human brain capillary bed during aging and atherosclerosis, Zh. nevropatol. i psihiatrii. 1984. Vol. 76, No. 7. P. 991–993.
  24. Chertok V.M., Pigolkin Ju.I. Structural changes of the brain soft membrane endarterium in atherosclerosis, Zh. nevropatol. i psihiatrii. 1987. Vol. 82, No. 7. P. 992–995.
  25. Chertok V.M., Pigolkin Ju.I., Motavkin P.A. The comparative researches of cholinergic and adrenergic innervation into hu man and some animals brain, Arh. anat., gistol. i jembriol. 1989. Vol. 96, No. 4. P. 28–33.
  26. Chertok V.M., Kocjuba A.E., Bespalova E.P. The role of nitric oxide in the reaction of blood vessels to laser irradiation, Bull. eksperim. biol. i med. 2008. Vol. 145, No. 6. P. 699–703.
  27. Chertok V.M., Kocjuba A.E.NO‑positive neurons in some nuclei of human bulbar vasomotor under hypertension, Bjull. jeksperim. biol. i med. 2009. Vol. 147, No. 5. P. 571–575. 
  28. Chertok V.M., Kocjuba A.E. Nitric oxide in the mechanisms of the cerebral afferent innervation arteries, Citologija. 2010. Vol. 52, No. 1. P. 24–29.
  29. Chertok V.M., Kocjuba A.E. The receptor system of human brain vascular under hypertension, Zh. nevropatol. i psihiatrii. 2010. No. 10. P. 40–47.
  30. Chertok V.M., Kocjuba A.E., Babich E.V. The intima ultrastructure of the human pial arteries under hypertension, Morfologija. 2009. No. 5. P. 50–54.
  31. Chertok V.M., Kocjuba A.E. Age‑related changes of ergic neurons in some medulla oblongata nuclei of rat, Ontogenez. 2010. Vol. 41, No. 3. P. 1–9.
  32. Chertok V.M., Kocjuba A.E., Kocjuba E.P. Serotonin and nitroxidergic medulla neurons in rats, Morfologija. 2011. No. 1. P. 32–37.
  33. Achouh P.E., Simonet S., Fabiani J.‑N., Verbeuren T.J. Carbon monoxide induces relaxation of human internal thoracic and radial arterial grafts, Interactive CardioVascular and Thoracic Surgery. 2008. Vol. 7, Nо. 6. Р. 959 ‑ 962.
  34. Ali M.Y., Ping C.Y., Mok Y.Y. et al. Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide? Br. J. Pharmacol. 2006. Vol. 149. P. 625–634.
  35. Andresen J.J., Shafi N.I., Durante W., Bryan R.M. Effects of carbon monoxide and heme oxygenase inhibitors in cerebral vessels of rats and mice, Am. J. Physiol. Heart. Circ. Physiol. 2006. Vol. 291. P.H223–H230.
  36. Becker B.F., Heindl B., Kupatt C., Zahler S. Endothelial function and hemostasis, Z. Kardiol. 2000. Vol. 89, Nо. 7. Р. 160.
  37. Beckman J., Beckman T., Chen J. et al. Apparent hydroxyl radical production by peroxynitrite: implication for endothelial injury from nitric oxide and superoxide, Proc. Natl. Acad. Sci. USA. 1990. Vol. 87. P. 1620–1622.
  38. Bellian J., Thuillez C., Joannides R. Contributon of endothelium‑derived hyperpolarizing factors to the regulation of vascular tone in humans, Fundam. Clin. Fharmacol. 2008. Vol. 22. P. 363–377.
  39. Bergeron M., Ferriero D.M., Vreman H.J. et al. Hypoxia‑ischemia, but not hypoxia alone, induces the expression of heme oxygenase‑1 (HSP32) in newborn rat brain. J. Cereb. Blood Flow Metab. 1997. Vol. 17. Р.647–658.
  40. Boo Y.C., Jo H. Flow‑dependent regulation of endothelial nitric oxide synthase: role of protein kinases. Am. J. Physiol. Cell Physiol. 2003. Vol. 285, Nо. 3. Р. 499–508.
  41. Brandes R.P., Schmitz‑Winnenthal F.H., Félétou M. et al. An endothelium‑dependent hyperpolarizing factor distinct from NO and prostacyclin is major endothelium‑dependent vasodilator in resistant vessels of wild‑type and endothelial NO syntase knockout mice, Proc. Natl. Acad. Sci. USA. 2000. Vol. 97. P. 9747–9752.
  42. Brian J. E., Heistad D.D., Faraci F.M. Effect of carbon monoxide on rabbit cerebral arteries, Stroke. 1994. Vol. 25. Р. 639–644.
  43. Catalano C., Rastelli S. Blood pressure control: hydrogen sulfide, a new gasotransmitter, takes stage, Nephrol. Dial. Transpl. 2009. Vol. 24, Nо. 5. Р. 1394–1396.
  44. Chen X., Jhee K.H., Kruger W.D. Production of the neuromodulator H2S by cystathionine beta‑synthase via the condensation of cysteine and homocysteine, J. Biol. Chem. 2004. Vol. 279. P. 52082–52086.
  45. Cheng Y., Ndisang J.F., Tang G. et al. Hydrogen sulfide‑induced relaxation of resistance mesenteric artery beds of rats, Am. J. Physiol. Heart Circ. Physiol. 2004. Vol. 287. P. H2316–H2323.
  46. Chertok V.M., Kotsyuba A.E., Babich E.V. Nitroxidergic neurons in nuclei of human and rat medulla oblongata, Cell and Tissue Biology. 2009. Vol. 3, Nо. 4. P. 335–339.
  47. Cohen R.A., Adachi T. Nitric‑oxide‑induced vasodilatation: regulation by physiologic S‑glutathiolation and pathologic oxidation of the sarcoplasmic endoplasmic reticulum calcium ATPase, Trends Cardiovasc. Med. 2006. Vol. 16. Р. 109–114.
  48. Félétou M., Vanhoutte P. M.Endothelium‑derived hyperpolarization: past beliefs and present facts. Ann. Med. 2007. Vol. 39. P. 495–516.
  49. Fleming I., Busse R. Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase, Am. J. Physiol. Regul. Integr. Comp. Physiol. 2003. 284, No. 1. P. R1–12.
  50. Florey H.W. The endothelial cell, Br. Med. J. 1966. Vol. 2. P. 487–489. 
  51. Folkow B.W. Description of the miogenic hypothesis, Circ. Res. Vol. 14–15, suppl. 1. P. 279.
  52. Freedman J.E., Loscalzo J. Nitric oxide and its relationship to thrombotic disorders, J. Thromb. Haemost. 2003. Vol. 1, No. 6. Р. 1183–1188.
  53. Furchgott R.F., Zawadzki J.W. The obligatory role of endothelial cells in the relaxation of vascular smooth muscle by acetylcholine, Nature. 1980. Vol. 286. Р. 373–376.
  54. Gadalla M.M., Snayder S.H.Hydrogen sulfide as a gasotransmitter, J. Neurochem. 2010. Vol. 113. Р. 14–26.
  55. Gagov H., Kadinov B., Hristov K. et al. Role of constitutively expressed heme oxygenase‑2 in the regulation of guinea pig coronary artery tone, Pflügers Arch. Eur. J. of Physiol., 2003. Vol. 446, Nо. 4. P. 412–421.
  56. Gerova M., Smiesko V., Gero J., Batza E. Dilatation of conduit coronary artery induced by high blood flow, Physiol. Bohemoslov. 1983. Vol. 32, Nо. 1. P. 55 ‑ 63. 
  57. Graser T., Vedernikov Y.P., Li D.S. Study on the mechanism of carbon monoxide induced endothelium‑independent relaxation in porcine coronary artery and vein, Biomed. Biochim. Acta. 1990. Vol. 49. Р.293–296.
  58. Grossman J. D., Morgan J. P. Cardiovascular effects of endothelin, New Physiol. Sci. 1997. Vol. 12. P. 113–117.
  59. Hibbs J.D., Westenfelder C., Taintor R. et al. Evidence for cytokine‑inducible nitric oxide synthesis from L‑arginine in patients receiving interleukin‑2 therapy, J. Clin. Invest. 1992. Vol. 89. Р. 867–877.
  60. Hosoki R., Matsuki N., Kimura H. The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide, Biochem. Biophys. Res. Commun. 1997. Vol. 237. Р. 527–531.
  61. Imai T., Morita T., Shindo T. et al. Vascular smooth muscle cell‑directed overexpression of heme oxygenase‑1 elevates blood pressure through attenuation of nitric oxide‑induced vasodilation in mice, Circ Res. 2001. Vol. 89. Р. 55–62.
  62. Ishikawa M., Kajimura M., Adachi T., Maruyama K.Carbon monoxide from heme oxygenase‑2 is a tonic regulator against NO‑dependent vasodilatation in the adult rat cerebral microcirculation, Circ. Res. 2005. Vol. 97. Р. 104–119.
  63. Jones W., Durante W., Korthuis R.J. Heme Oxygenase‑1deficiency leads to alteration of soluble guanylate cyclase redox regulation, J. Pharmacol. Exp. Ther. 2010. Vol. 335, Nо. 1. Р. 85–91.
  64. Johnson FK, Johnson RA. Carbon monoxide promotes endothelium‑dependent constriction of isolated gracilis muscle arterioles, Am. J. Physiol. Regul. Integr. Comp. Physiol. 2003. Vol. 285. P. R536–R541.
  65. Kanu A., Whitfield J., Leffler C.W. Carbon monoxide contributes to hypotension‑induced cerebrovascular vasodilation in piglets, Am. J. Physiol. Heart Circ. Physiol. 2006. Vol. 291, Nо. 5. P. H2409–H2414.
  66. Leffler C.W., Nasjletti A., Yu C. et al. Carbon monoxide and cerebral microvascular tone in newborn pigs, Am. J. Physiol. Heart Circ. Physiol. 1999. Vol. 276. P. H1641–H1646.
  67. Luksha L., Agewall S., Kublickiene K. Endothelium‑derived hyperpolarizing factor in vascular physiology and cardiovascular disease, Atherosclerosis, 2009. Vol. 202. P. 330–334.
  68. Mathai J. C., Missner A., Kugler P. et al. Nо. facilitator required for membrane transport of hydrogen sulfide, PNAS. 2009. Vol. 106. Р. 16633–16638.
  69. Maulik N., Engelman D.T., Watanabe M. et al. Nitric oxide a retrograde messenger for carbon monoxide signaling in ischemic heart, Mol. Cell. Biochem. 1996. Vol. 157, Nо. 1–2. P. 75–86.
  70. Meredeth J. E, Fazeli B, Schwartz M.A. The extracellular matrix as a mediator of apoptosis, Mol. Biol. Cell, 1993. Nо. 4. P. H953–961.
  71. Meyer J. S., Gotoh F. Interaction of cerebral hemodynamics and metabolism, Neurology. 1961. Vol. 11. P. 46–65.
  72. Mustafa A.K., Gadalla M.M., Snyder S.H. Signaling by Gasotransmitters, Sci. Signal. 2009. Vol. 2, Nо. 68. P. 2.
  73. Naik J.S., Walker B.R.Heme‑oxygenase‑mediated vasodilation involves vascular smooth muscle cell hyperpolarization, Am. J. Physiol. Heart Circ. Physiol. 2003. Vol. 285. P. H220–H228.
  74. Nakaki T.Physiological and clinical significance of NO (nitric oxide) – a review, Keio J. Med. 1994. Vol. 43. Р. 15–26.
  75. Nathan C., Xie Q. Nitric oxide synthases: roles, tolls and controls, Cell. 1994. Vol. 79. Р.915–918.
  76. Nussler A.K., Di S.M., Billiar T.R. et al. Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin, J. Exp. Med. 1992. Vol. 176. Р. 261–264.
  77. Qin X., Kwansa H., Bucci E. et al. Role of heme oxygenase‑2 in pial arteriolar response to acetylcholine in mice with and without transfusion of cell‑free hemoglobin polymers, Am. J. Physiol. Regul. Integr. Comp. Physiol. 2008. Vol. 295. P. R498–R504.
  78. Palmer R.M.J., Ferrige A.G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium‑derived relaxing factor, Nature. 1987. Vol. 327. Р. 534–526.
  79. Reivich M. Arterial pCO2 and cerebral hemodynamics, Am. J. Physiol. 1964. Vol. 206. P. 25–35.
  80. Rodbard S.Vascular modifications induced by flow, Am. Heart. J. 1956. Vol. 51. P. 926.
  81. Rodbard S.Dynamics of blood flow in stenotic vascular lesions, Am. Heart. J. 1966. Vol. 72. P. 698–704.
  82. Shibuya N., Mikami Y., Kimura Y. et al. Expresses 3–mercaptopyruvate sulfurtransferase and produces hydrogen sulfide, J. Biochem. 2009. Vol. 146, N 5. Р.623–626.
  83. Takeda A., Onodera H., Sugimoto A. et al. Increased expression of heme oxygenase mRNA in rat brain following transient forebrain ischemia, Brain Res. 1994. Vol. 666, Nо. 1. P. 120–124.
  84. Toda N., Ayajiki K., Okamura T. Cerebral blood flow regulation by nitric oxide: recent advances, Pharmacol. Rev. 2009. Vol. 61, Nо. 1. Р. 62–97.
  85. Toda N., Okamura T. Modulation of renal blood flow and vascular tone by neuronal nitric oxide synthase‑derived nitric oxide, J. Vasc. Res. 2011. Vol. 48, Nо. 1. Р. 1–10.
  86. Vanhoutte P. M., Mombouli J.V. Vascular endothelium: vasoactive mediators, Prog. Cardiovase. Dis. 1996. Vol. 39. Р. 229–238.
  87. Walford G., Loscalzo J. Nitric oxide in vascular biology, J. Thromb. Haemost. 2003. Vol. 1, Nо. 10. Р. 2112–2118.
  88. Wang R. Two's company, three's a crowd: can H2S be the third endoge. us gaseous transmitter? FASEB J. 2002. Vol. 16. P. 1792–1798.
  89. Wang R., Wang Z., Wu L. Carbon monoxide‑induced vasorelaxation and the underlying mechanisms, Br. J. Pharmacol. 1997. Vol. 121. P. 927–934.
  90. Wedgwood S., Black S.M. Endothelial 1 decreases endothelial NOS expression and activity through ETA receptor‑mediated generation of hydrogen peroxide, Am. J. Physiol. Lung. Cell. Mol. Physiol. 2005. Vol. 288, Nо. 3. P. 480–487.
  91. Yanagisawa M., Kurihara H., Kimura S., Goto K., Masaki T.A novel peptide vasoconstictor, endothelin, is produced by vascular endothelium and modulates smooth muscle Ca2+ channels, J. Нypertens. 1988. Vol. 6. P. 188 ‑191.
  92. Yang G., Wu L., Jiang B. et al. H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine γ‑lyase, Science. 2008. Vol. 322. Р. 587–590.
  93. Zhao W., Zhang J., Lu Y., Wang R. The vasorelaxant effect of H(2) S as a novel endogenous gaseous K (ATP) channel opener, EMBO J. 2001. Vol. 20. Р. 6008–6016 
  94. Zhao W., Wang R. H2 S‑induced vasorelaxation and underlying cellular and molecular mechanisms, Am. J. Physiol. Heart Circ. Physiol. 2002. Vol. 283. P. H474–480.
  95. Zoccali C., Catalano C., Rastelli S. Blood pressure control: hydrogen sulfide, a new gasotransmitter, takes stage, Nephrol. Dial. Transplant. 2009. Vol. 24. Р. 1394–1396.
  96. Zhong G., Chen F., Cheng Y. et al. The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase, J. Hypertens. 2003. Vol. 21. P. 1879–1885.


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