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. 1995 Sep;116(2):1815–1820. doi: 10.1111/j.1476-5381.1995.tb16668.x

Effects of nicorandil on the recovery of reflex potentials after spinal cord ischaemia in cats.

T Suzuki 1, T Sekikawa 1, T Nemoto 1, H Moriya 1, H Nakaya 1
PMCID: PMC1909092  PMID: 8528565

Abstract

1. The pathophysiological significance of ATP-sensitive K+ (KATP) channels in the central nervous system is not fully understood. In this study the effects of nicorandil (a hybrid vasodilator having a dual mechanism of action as a K+ channel opener and a nitrate) on the recovery of the spinal cord reflex potentials after spinal cord ischaemia were examined and compared with those of pinacidil and nitroprusside in anaesthetized spinal cats. 2. Spinal cord ischaemia was produced by occlusion of the thoracic aorta and the bilateral internal mammary arteries for 10 min. Regional blood flow in the spinal cord was continuously measured with a laser-Doppler flow meter. The monosynaptic (MSR) and polysynaptic reflex (PSR) potentials, elicited by electrical stimulation of the tibial nerve, were recorded from the lumbo-sacral ventral root. The recovery process of spinal reflex potentials was reproducible when the occlusion was repeated twice at an interval of 120 min. 3. Pretreatment with nicorandil (30-100 micrograms kg-1) accelerated the recovery of PSR potentials after spinal cord ischaemia. Such an accelerating effect on the recovery of PSR potentials was also shared by pinacidil (100 micrograms kg-1), another K+ channel opener. In addition, the accelerating effect of nicorandil (100 micrograms kg-1) on the recovery of PSR potentials was abolished by co-administration of glibenclamide (3 mg kg-1), a sulphonylurea KATP channel blocker. Nitroprusside (8 micrograms kg-1min-1) retarded rather than improved the recovery of PSR potentials after spinal cord ischaemia. All of these drugs failed to improve the spinal cord blood flow during ischaemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Ahlner J., Andersson R. G., Torfgård K., Axelsson K. L. Organic nitrate esters: clinical use and mechanisms of actions. Pharmacol Rev. 1991 Sep;43(3):351–423. [PubMed] [Google Scholar]
  2. Amoroso S., Schmid-Antomarchi H., Fosset M., Lazdunski M. Glucose, sulfonylureas, and neurotransmitter release: role of ATP-sensitive K+ channels. Science. 1990 Feb 16;247(4944):852–854. doi: 10.1126/science.2305257. [DOI] [PubMed] [Google Scholar]
  3. Ashcroft F. M. Adenosine 5'-triphosphate-sensitive potassium channels. Annu Rev Neurosci. 1988;11:97–118. doi: 10.1146/annurev.ne.11.030188.000525. [DOI] [PubMed] [Google Scholar]
  4. Ashford M. L., Sturgess N. C., Trout N. J., Gardner N. J., Hales C. N. Adenosine-5'-triphosphate-sensitive ion channels in neonatal rat cultured central neurones. Pflugers Arch. 1988 Aug;412(3):297–304. doi: 10.1007/BF00582512. [DOI] [PubMed] [Google Scholar]
  5. Auchampach J. A., Cavero I., Gross G. J. Nicorandil attenuates myocardial dysfunction associated with transient ischemia by opening ATP-dependent potassium channels. J Cardiovasc Pharmacol. 1992;20(5):765–771. [PubMed] [Google Scholar]
  6. Ben-Ari Y., Krnjević K., Crépel V. Activators of ATP-sensitive K+ channels reduce anoxic depolarization in CA3 hippocampal neurons. Neuroscience. 1990;37(1):55–60. doi: 10.1016/0306-4522(90)90191-6. [DOI] [PubMed] [Google Scholar]
  7. Bernardi H., Fosset M., Lazdunski M. Characterization, purification, and affinity labeling of the brain [3H]glibenclamide-binding protein, a putative neuronal ATP-regulated K+ channel. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9816–9820. doi: 10.1073/pnas.85.24.9816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cole W. C., McPherson C. D., Sontag D. ATP-regulated K+ channels protect the myocardium against ischemia/reperfusion damage. Circ Res. 1991 Sep;69(3):571–581. doi: 10.1161/01.res.69.3.571. [DOI] [PubMed] [Google Scholar]
  9. Czéh G., Somjen G. G. Hypoxic failure of synaptic transmission in the isolated spinal cord, and the effects of divalent cations. Brain Res. 1990 Sep 17;527(2):224–233. doi: 10.1016/0006-8993(90)91141-3. [DOI] [PubMed] [Google Scholar]
  10. Ducker T. B., Salcman M., Lucas J. T., Garrison W. B., Perot P. L., Jr Experimental spinal cord trauma, II: Blood flow, tissue oxygen, evoked potentials in both paretic and plegic monkeys. Surg Neurol. 1978 Jul;10(1):64–70. [PubMed] [Google Scholar]
  11. Ducker T. B., Salcman M., Perot P. L., Jr, Ballantine D. Experimental spinal cord trauma, I: Correlation of blood flow, tissue oxygen and neurologic status in the dog. Surg Neurol. 1978 Jul;10(1):60–63. [PubMed] [Google Scholar]
  12. Edwards G., Weston A. H. The pharmacology of ATP-sensitive potassium channels. Annu Rev Pharmacol Toxicol. 1993;33:597–637. doi: 10.1146/annurev.pa.33.040193.003121. [DOI] [PubMed] [Google Scholar]
  13. Faraci F. M., Brian J. E., Jr Nitric oxide and the cerebral circulation. Stroke. 1994 Mar;25(3):692–703. doi: 10.1161/01.str.25.3.692. [DOI] [PubMed] [Google Scholar]
  14. Gross G. J., Warltier D. C., Hardman H. F. Comparative effects of nicorandil, a nicotinamide nitrate derivative, and nifedipine on myocardial reperfusion injury in dogs. J Cardiovasc Pharmacol. 1987 Nov;10(5):535–542. doi: 10.1097/00005344-198711000-00007. [DOI] [PubMed] [Google Scholar]
  15. Grover G. J., Sleph P. G., Parham C. S. Nicorandil improves postischemic contractile function independently of direct myocardial effects. J Cardiovasc Pharmacol. 1990 May;15(5):698–705. doi: 10.1097/00005344-199005000-00003. [DOI] [PubMed] [Google Scholar]
  16. Homma S., Suzuki T., Murayama S., Otsuka M. Amino acid and substance P contents in spinal cord of cats with experimental hind-limb rigidity produced by occlusion of spinal cord blood supply. J Neurochem. 1979 Mar;32(3):691–698. doi: 10.1111/j.1471-4159.1979.tb04551.x. [DOI] [PubMed] [Google Scholar]
  17. Jiang C., Xia Y., Haddad G. G. Role of ATP-sensitive K+ channels during anoxia: major differences between rat (newborn and adult) and turtle neurons. J Physiol. 1992 Mar;448:599–612. doi: 10.1113/jphysiol.1992.sp019060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kader A., Frazzini V. I., Solomon R. A., Trifiletti R. R. Nitric oxide production during focal cerebral ischemia in rats. Stroke. 1993 Nov;24(11):1709–1716. doi: 10.1161/01.str.24.11.1709. [DOI] [PubMed] [Google Scholar]
  19. Kurihara J., Ochiai N., Kato H. Protection by nicorandil against the dysfunction of the central vagal baroreflex system following transient global cerebral ischaemia in dogs. Br J Pharmacol. 1993 Aug;109(4):1263–1267. doi: 10.1111/j.1476-5381.1993.tb13758.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lamping K. A., Christensen C. W., Pelc L. R., Warltier D. C., Gross G. J. Effects of nicorandil and nifedipine on protection of ischemic myocardium. J Cardiovasc Pharmacol. 1984 May-Jun;6(3):536–542. doi: 10.1097/00005344-198405000-00024. [DOI] [PubMed] [Google Scholar]
  21. MURAYAMA S., SMITH C. M. RIGIDITY OF HIND LIMBS OF CATS PRODUCED BY OCCLUSION OF SPINAL CORD BLOOD SUPPLY. Neurology. 1965 Jun;15:565–577. doi: 10.1212/wnl.15.6.577. [DOI] [PubMed] [Google Scholar]
  22. Martiniak J., Saganová K., Chavko M. Free and peptide-bound amino acids as indicators of ischemic damage of the rabbit spinal cord. J Neuropathol Exp Neurol. 1991 Jan;50(1):73–81. doi: 10.1097/00005072-199101000-00006. [DOI] [PubMed] [Google Scholar]
  23. Miller J. A., Velayo N. L., Dage R. C., Rampe D. High affinity [3H]glibenclamide binding sites in rat neuronal and cardiac tissue: localization and developmental characteristics. J Pharmacol Exp Ther. 1991 Jan;256(1):358–364. [PubMed] [Google Scholar]
  24. Mourre C., Ben Ari Y., Bernardi H., Fosset M., Lazdunski M. Antidiabetic sulfonylureas: localization of binding sites in the brain and effects on the hyperpolarization induced by anoxia in hippocampal slices. Brain Res. 1989 May 1;486(1):159–164. doi: 10.1016/0006-8993(89)91288-2. [DOI] [PubMed] [Google Scholar]
  25. Mourre C., Widmann C., Lazdunski M. Sulfonylurea binding sites associated with ATP-regulated K+ channels in the central nervous system: autoradiographic analysis of their distribution and ontogenesis, and of their localization in mutant mice cerebellum. Brain Res. 1990 Jun 11;519(1-2):29–43. doi: 10.1016/0006-8993(90)90057-i. [DOI] [PubMed] [Google Scholar]
  26. Murphy K. P., Greenfield S. A. ATP-sensitive potassium channels counteract anoxia in neurones of the substantia nigra. Exp Brain Res. 1991;84(2):355–358. doi: 10.1007/BF00231456. [DOI] [PubMed] [Google Scholar]
  27. Nakaya H., Takeda Y., Tohse N., Kanno M. Effects of ATP-sensitive K+ channel blockers on the action potential shortening in hypoxic and ischaemic myocardium. Br J Pharmacol. 1991 May;103(1):1019–1026. doi: 10.1111/j.1476-5381.1991.tb12294.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Noma A. ATP-regulated K+ channels in cardiac muscle. Nature. 1983 Sep 8;305(5930):147–148. doi: 10.1038/305147a0. [DOI] [PubMed] [Google Scholar]
  29. Nowicki J. P., Duval D., Poignet H., Scatton B. Nitric oxide mediates neuronal death after focal cerebral ischemia in the mouse. Eur J Pharmacol. 1991 Nov 12;204(3):339–340. doi: 10.1016/0014-2999(91)90862-k. [DOI] [PubMed] [Google Scholar]
  30. Ohta H., Jinno Y., Harada K., Ogawa N., Fukushima H., Nishikori K. Cardioprotective effects of KRN2391 and nicorandil on ischemic dysfunction in perfused rat heart. Eur J Pharmacol. 1991 Nov 5;204(2):171–177. doi: 10.1016/0014-2999(91)90702-r. [DOI] [PubMed] [Google Scholar]
  31. Rorsman P., Trube G. Glucose dependent K+-channels in pancreatic beta-cells are regulated by intracellular ATP. Pflugers Arch. 1985 Dec;405(4):305–309. doi: 10.1007/BF00595682. [DOI] [PubMed] [Google Scholar]
  32. Schmid-Antomarchi H., Amoroso S., Fosset M., Lazdunski M. K+ channel openers activate brain sulfonylurea-sensitive K+ channels and block neurosecretion. Proc Natl Acad Sci U S A. 1990 May;87(9):3489–3492. doi: 10.1073/pnas.87.9.3489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Spruce A. E., Standen N. B., Stanfield P. R. Voltage-dependent ATP-sensitive potassium channels of skeletal muscle membrane. Nature. 1985 Aug 22;316(6030):736–738. doi: 10.1038/316736a0. [DOI] [PubMed] [Google Scholar]
  34. Standen N. B., Quayle J. M., Davies N. W., Brayden J. E., Huang Y., Nelson M. T. Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science. 1989 Jul 14;245(4914):177–180. doi: 10.1126/science.2501869. [DOI] [PubMed] [Google Scholar]
  35. Taira N. Nicorandil as a hybrid between nitrates and potassium channel activators. Am J Cardiol. 1989 Jun 20;63(21):18J–24J. doi: 10.1016/0002-9149(89)90200-2. [DOI] [PubMed] [Google Scholar]
  36. Urbán L., Somjen G. G. Reversible effects of hypoxia on neurons in mouse dorsal root ganglia in vitro. Brain Res. 1990 Jun 18;520(1-2):36–42. doi: 10.1016/0006-8993(90)91689-e. [DOI] [PubMed] [Google Scholar]
  37. Zhang A. L., Hao J. X., Seiger A., Xu X. J., Wiesenfeld-Hallin Z., Grant G., Aldskogius H. Decreased GABA immunoreactivity in spinal cord dorsal horn neurons after transient spinal cord ischemia in the rat. Brain Res. 1994 Sep 5;656(1):187–190. doi: 10.1016/0006-8993(94)91383-8. [DOI] [PubMed] [Google Scholar]

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