Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Jul;115(6):889–894. doi: 10.1111/j.1476-5381.1995.tb15893.x

Substance P-induced relaxation and hyperpolarization in human cerebral arteries.

J Petersson 1, P M Zygmunt 1, L Brandt 1, E D Högestätt 1
PMCID: PMC1908996  PMID: 7582516

Abstract

1. Vascular effects of substance P were studied in human isolated pial arteries removed from 14 patients undergoing cerebral cortical resection. 2. Substance P induced a concentration-dependent relaxation in the presence of indomethacin. No relaxation was seen in arteries where the endothelium had been removed. 3. N omega-nitro-L-arginine (L-NOARG, 0.3 mM) abolished the relaxation in arteries from six patients. The relaxation was only partially inhibited in the remaining eight patients, the reduction of the maximum relaxation being less than 50% in each patient. 4. The L-NOARG-resistant relaxation was abolished when the external K+ concentration was raised above 30 mM. 5. Substance P caused a smooth muscle hyperpolarization (in the presence of L-NOARG and indomethacin), but only when the artery showed an L-NOARG-resistant relaxation. 6. The results indicate that nitric oxide is an important mediator of endothelium-dependent relaxation in human cerebral arteries. Furthermore, another endothelium-dependent pathway, causing hyperpolarization and vasodilatation, was identified in arteries from more than half the population of patients.

Full text

PDF
889

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adeagbo A. S., Triggle C. R. Varying extracellular [K+]: a functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed. J Cardiovasc Pharmacol. 1993 Mar;21(3):423–429. [PubMed] [Google Scholar]
  2. Akopov S. E., Grigorian M. R., Gabrielian E. S. The endothelium-dependent relaxation of human middle cerebral artery: effects of activated neutrophils. Experientia. 1992 Jan 15;48(1):34–36. doi: 10.1007/BF01923601. [DOI] [PubMed] [Google Scholar]
  3. Angus J. A., Cocks T. M. Endothelium-derived relaxing factor. Pharmacol Ther. 1989;41(1-2):303–352. doi: 10.1016/0163-7258(89)90112-5. [DOI] [PubMed] [Google Scholar]
  4. Brandt L., Ljunggren B., Andersson K. E., Hindfelt B. Individual variations in response of human cerebral arterioles to vasoactive substances, human plasma, and CSF from patients with aneurysmal SAH. J Neurosurg. 1981 Sep;55(3):431–437. doi: 10.3171/jns.1981.55.3.0431. [DOI] [PubMed] [Google Scholar]
  5. Brayden J. E. Membrane hyperpolarization is a mechanism of endothelium-dependent cerebral vasodilation. Am J Physiol. 1990 Sep;259(3 Pt 2):H668–H673. doi: 10.1152/ajpheart.1990.259.3.H668. [DOI] [PubMed] [Google Scholar]
  6. Brayden J. E., Wellman G. C. Endothelium-dependent dilation of feline cerebral arteries: role of membrane potential and cyclic nucleotides. J Cereb Blood Flow Metab. 1989 Jun;9(3):256–263. doi: 10.1038/jcbfm.1989.42. [DOI] [PubMed] [Google Scholar]
  7. Chester A. H., O'Neil G. S., Tadjkarimi S., Palmer R. M., Moncada S., Yacoub M. H. The role of nitric oxide in mediating endothelium dependent relaxations in the human epicardial coronary artery. Int J Cardiol. 1990 Dec;29(3):305–309. doi: 10.1016/0167-5273(90)90118-o. [DOI] [PubMed] [Google Scholar]
  8. Conde M. V., Marco E. J., Fraile M. L., Benito J. M., Moreno M. J., Sanz M. L., López de Pablo A. L. Different influence of endothelium in the mechanical responses of human and cat isolated cerebral arteries to several agents. J Pharm Pharmacol. 1991 Apr;43(4):255–261. doi: 10.1111/j.2042-7158.1991.tb06679.x. [DOI] [PubMed] [Google Scholar]
  9. Cowan C. L., Palacino J. J., Najibi S., Cohen R. A. Potassium channel-mediated relaxation to acetylcholine in rabbit arteries. J Pharmacol Exp Ther. 1993 Sep;266(3):1482–1489. [PubMed] [Google Scholar]
  10. Edwards F. R., Hirst G. D., Silverberg G. D. Inward rectification in rat cerebral arterioles; involvement of potassium ions in autoregulation. J Physiol. 1988 Oct;404:455–466. doi: 10.1113/jphysiol.1988.sp017299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Faraci F. M. Endothelium-derived vasoactive factors and regulation of the cerebral circulation. Neurosurgery. 1993 Oct;33(4):648–659. doi: 10.1227/00006123-199310000-00014. [DOI] [PubMed] [Google Scholar]
  12. Faraci F. M. Regulation of the cerebral circulation by endothelium. Pharmacol Ther. 1992;56(1):1–22. doi: 10.1016/0163-7258(92)90035-x. [DOI] [PubMed] [Google Scholar]
  13. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  14. Hardebo J. E., Kåhrström J., Owman C., Salford L. G. Endothelium-dependent relaxation by uridine tri- and diphosphate in isolated human pial vessels. Blood Vessels. 1987;24(3):150–155. doi: 10.1159/000158690. [DOI] [PubMed] [Google Scholar]
  15. Harder D. R. Comparison of electrical properties of middle cerebral and mesenteric artery in cat. Am J Physiol. 1980 Jul;239(1):C23–C26. doi: 10.1152/ajpcell.1980.239.1.C23. [DOI] [PubMed] [Google Scholar]
  16. Hatake K., Kakishita E., Wakabayashi I., Sakiyama N., Hishida S. Effect of aging on endothelium-dependent vascular relaxation of isolated human basilar artery to thrombin and bradykinin. Stroke. 1990 Jul;21(7):1039–1043. doi: 10.1161/01.str.21.7.1039. [DOI] [PubMed] [Google Scholar]
  17. Högestätt E. D., Andersson K. E., Edvinsson L. Mechanical properties of rat cerebral arteries as studied by a sensitive device for recording of mechanical activity in isolated small blood vessels. Acta Physiol Scand. 1983 Jan;117(1):49–61. doi: 10.1111/j.1748-1716.1983.tb07178.x. [DOI] [PubMed] [Google Scholar]
  18. Iadecola C., Pelligrino D. A., Moskowitz M. A., Lassen N. A. Nitric oxide synthase inhibition and cerebrovascular regulation. J Cereb Blood Flow Metab. 1994 Mar;14(2):175–192. doi: 10.1038/jcbfm.1994.25. [DOI] [PubMed] [Google Scholar]
  19. Kanamaru K., Waga S., Fujimoto K., Itoh H., Kubo Y. Endothelium-dependent relaxation of human basilar arteries. Stroke. 1989 Sep;20(9):1208–1211. doi: 10.1161/01.str.20.9.1208. [DOI] [PubMed] [Google Scholar]
  20. Luscher T. F., Vanhoutte P. M. Endothelium-dependent responses in human blood vessels. Trends Pharmacol Sci. 1988 May;9(5):181–184. doi: 10.1016/0165-6147(88)90035-1. [DOI] [PubMed] [Google Scholar]
  21. Martín de Aguilera E., Vila J. M., Irurzun A., Martínez M. C., Martínez Cuesta M. A., Lluch S. Endothelium-independent contractions of human cerebral arteries in response to vasopressin. Stroke. 1990 Dec;21(12):1689–1693. doi: 10.1161/01.str.21.12.1689. [DOI] [PubMed] [Google Scholar]
  22. Moncada S. Eighth Gaddum Memorial Lecture. University of London Institute of Education, December 1980. Biological importance of prostacyclin. Br J Pharmacol. 1982 May;76(1):3–31. doi: 10.1111/j.1476-5381.1982.tb09186.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mulvany M. J., Halpern W. Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res. 1977 Jul;41(1):19–26. doi: 10.1161/01.res.41.1.19. [DOI] [PubMed] [Google Scholar]
  24. Myers P. R., Minor R. L., Jr, Guerra R., Jr, Bates J. N., Harrison D. G. Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. Nature. 1990 May 10;345(6271):161–163. doi: 10.1038/345161a0. [DOI] [PubMed] [Google Scholar]
  25. Mülsch A., 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 Pharmacol. 1990 Jan-Feb;341(1-2):143–147. doi: 10.1007/BF00195071. [DOI] [PubMed] [Google Scholar]
  26. Nagao T., Vanhoutte P. M. Endothelium-derived hyperpolarizing factor and endothelium-dependent relaxations. Am J Respir Cell Mol Biol. 1993 Jan;8(1):1–6. doi: 10.1165/ajrcmb/8.1.1. [DOI] [PubMed] [Google Scholar]
  27. Nagao T., Vanhoutte P. M. Hyperpolarization as a mechanism for endothelium-dependent relaxations in the porcine coronary artery. J Physiol. 1992 Jan;445:355–367. doi: 10.1113/jphysiol.1992.sp018928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nagao T., Vanhoutte P. M. Hyperpolarization contributes to endothelium-dependent relaxations to acetylcholine in femoral veins of rats. Am J Physiol. 1991 Oct;261(4 Pt 2):H1034–H1037. doi: 10.1152/ajpheart.1991.261.4.H1034. [DOI] [PubMed] [Google Scholar]
  29. Nakashima M., Mombouli J. V., Taylor A. A., Vanhoutte P. M. Endothelium-dependent hyperpolarization caused by bradykinin in human coronary arteries. J Clin Invest. 1993 Dec;92(6):2867–2871. doi: 10.1172/JCI116907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nishiye E., Nakao K., Itoh T., Kuriyama H. Factors inducing endothelium-dependent relaxation in the guinea-pig basilar artery as estimated from the actions of haemoglobin. Br J Pharmacol. 1989 Mar;96(3):645–655. doi: 10.1111/j.1476-5381.1989.tb11864.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  32. Petersson J., Ryman T., Högestätt E. D. Enhancement of depolarization-induced contractions after endothelium denudation is not related to an impaired production of nitric oxide or prostacyclin in the rabbit basilar artery. Acta Physiol Scand. 1993 Dec;149(4):467–474. doi: 10.1111/j.1748-1716.1993.tb09644.x. [DOI] [PubMed] [Google Scholar]
  33. Plane F., Garland C. J. Differential effects of acetylcholine, nitric oxide and levcromakalim on smooth muscle membrane potential and tone in the rabbit basilar artery. Br J Pharmacol. 1993 Oct;110(2):651–656. doi: 10.1111/j.1476-5381.1993.tb13861.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Reuter H. Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature. 1983 Feb 17;301(5901):569–574. doi: 10.1038/301569a0. [DOI] [PubMed] [Google Scholar]
  35. Szabó C., Hardebo J. E., Salford L. G. Role of endothelium in the responses of human intracranial arteries to a slight reduction of extracellular magnesium. Exp Physiol. 1992 Jan;77(1):209–211. doi: 10.1113/expphysiol.1992.sp003575. [DOI] [PubMed] [Google Scholar]
  36. Toda N. Mechanism underlying responses to histamine of isolated monkey and human cerebral arteries. Am J Physiol. 1990 Feb;258(2 Pt 2):H311–H317. doi: 10.1152/ajpheart.1990.258.2.H311. [DOI] [PubMed] [Google Scholar]
  37. Whalley E. T., Amure Y. O., Lye R. H. Analysis of the mechanism of action of bradykinin on human basilar artery in vitro. Naunyn Schmiedebergs Arch Pharmacol. 1987 Apr;335(4):433–437. doi: 10.1007/BF00165559. [DOI] [PubMed] [Google Scholar]
  38. Zygmunt P. M., Grundemar L., Högestätt E. D. Endothelium-dependent relaxation resistant to N omega-nitro-L-arginine in the rat hepatic artery and aorta. Acta Physiol Scand. 1994 Sep;152(1):107–114. doi: 10.1111/j.1748-1716.1994.tb09789.x. [DOI] [PubMed] [Google Scholar]
  39. Zygmunt P. M., Waldeck K., Högestätt E. D. The endothelium mediates a nitric oxide-independent hyperpolarization and relaxation in the rat hepatic artery. Acta Physiol Scand. 1994 Dec;152(4):375–384. doi: 10.1111/j.1748-1716.1994.tb09819.x. [DOI] [PubMed] [Google Scholar]
  40. de Nucci G., Gryglewski R. J., Warner T. D., Vane J. R. Receptor-mediated release of endothelium-derived relaxing factor and prostacyclin from bovine aortic endothelial cells is coupled. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2334–2338. doi: 10.1073/pnas.85.7.2334. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES