Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Aug;109(4):1263–1267. doi: 10.1111/j.1476-5381.1993.tb13758.x

Protection by nicorandil against the dysfunction of the central vagal baroreflex system following transient global cerebral ischaemia in dogs.

J Kurihara 1, N Ochiai 1, H Kato 1
PMCID: PMC2175772  PMID: 8401937

Abstract

1. A possible cerebroprotective effect of nicorandil was investigated in a canine model of 5 min global cerebral ischaemia, and compared with protective effects of nitroglycerin and nicardipine. 2. Cerebral ischaemia was produced by occlusion of the left subclavian and the brachiocephalic arteries with preceding ligation of the intercostal arteries. The decrease in baroreflex sensitivity (BRS), measured by phenylephrine-induced reflex bradycardia, was used to assess the cerebroprotective effect. 3. Nicorandil (10 or 30 micrograms kg-1 min-1, i.v.), nitroglycerin (3 micrograms kg-1 min-1, i.v.) or nicardipine (0.3 micrograms kg-1 min-1, i.v.) were infused for 60 min just before ischaemia. Nitroglycerin and nicardipine decreased mean arterial blood pressure to an extent similar to that induced by the lower dose of nicorandil. Blood flow in the dorsal medulla oblongata was increased by nicorandil and nicardipine, but not by nitroglycerin. 4. Nicorandil at both doses and nitroglycerin prevented the post-ischaemic decrease in BRS. In these cases, bilateral vagotomy during the reperfusion period decreased BRS, indicating that the vagal component of BRS was protected from ischaemia. On the other hand, nicardipine failed to exert a cerebroprotective effect. 5. The present study suggests that nicorandil may possess a direct cerebroprotective effect and that its property as a nitrate might, at least in part, be important for the observed cerebral protection.

Full text

PDF
1263

Selected References

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

  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. 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]
  3. 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]
  4. Furukawa K., Itoh T., Kajiwara M., Kitamura K., Suzuki H., Ito Y., Kuriyama H. Vasodilating actions of 2-nicotinamidoethyl nitrate on porcine and guinea-pig coronary arteries. J Pharmacol Exp Ther. 1981 Jul;218(1):248–259. [PubMed] [Google Scholar]
  5. Garthwaite G., Garthwaite J. Cyclic GMP and cell death in rat cerebellar slices. Neuroscience. 1988 Jul;26(1):321–326. doi: 10.1016/0306-4522(88)90148-0. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Holzmann S. Cyclic GMP as possible mediator of coronary arterial relaxation by nicorandil (SG-75). J Cardiovasc Pharmacol. 1983 May-Jun;5(3):364–370. doi: 10.1097/00005344-198305000-00004. [DOI] [PubMed] [Google Scholar]
  9. Kukovetz W. R., Holzmann S., Braida C., Pöch G. Dual mechanism of the relaxing effect of nicorandil by stimulation of cyclic GMP formation and by hyperpolarization. J Cardiovasc Pharmacol. 1991 Apr;17(4):627–633. doi: 10.1097/00005344-199104000-00016. [DOI] [PubMed] [Google Scholar]
  10. Kurihara J., Nishimura H., Oda N., Kato H. Deterioration of baroreceptor reflex by transient global cerebral ischemia in dogs. Jpn J Pharmacol. 1989 Feb;49(2):255–265. doi: 10.1254/jjp.49.255. [DOI] [PubMed] [Google Scholar]
  11. Kurihara J., Oda N., Kato H. Effect of flunarizine on the attenuation of baroreflex by transient cerebral ischemia. Eur J Pharmacol. 1989 Jun 8;165(1):147–150. doi: 10.1016/0014-2999(89)90781-4. [DOI] [PubMed] [Google Scholar]
  12. Kurihara J., Sahara T., Kato H. Deterioration of baroreflex by transient global cerebral ischemia: its correlation with the degree of ischemia or post-ischemic hypoperfusion in the medulla oblongata. Jpn J Pharmacol. 1989 Dec;51(4):493–499. doi: 10.1254/jjp.51.493. [DOI] [PubMed] [Google Scholar]
  13. Kurihara J., Sahara T., Kato H. Protective effect of beraprost sodium, a new chemically stable prostacyclin analogue, against the deterioration of baroreceptor reflex following transient global cerebral ischaemia in dogs. Br J Pharmacol. 1990 Jan;99(1):91–96. doi: 10.1111/j.1476-5381.1990.tb14659.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kurihara J., Sahara T., Oda N., Tomita H., Kato H. Selective dysfunction of the vagal component of the baroreflex following cerebral ischemia: protection by ifenprodil and flunarizine. Eur J Pharmacol. 1990 Nov 6;190(1-2):23–30. doi: 10.1016/0014-2999(90)94108-a. [DOI] [PubMed] [Google Scholar]
  15. Kurihara J., Tomita H., Ochiai N., Kato H. Protection by halothane of the vagal baroreflex system from transient global cerebral ischemia in dogs. Jpn J Pharmacol. 1992 Sep;60(1):63–66. doi: 10.1254/jjp.60.63. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Masuda Y., Ochi Y., Ochi Y., Karasawa T., Hatano N., Kadokawa T., Shimizu M. Protective effect of prostaglandins D2, E1 and I2 against cerebral hypoxia/anoxia in mice. Naunyn Schmiedebergs Arch Pharmacol. 1986 Nov;334(3):282–289. doi: 10.1007/BF00508783. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Nakagawa Y., Takeda K., Katano Y., Tsukada T., Kitagawa T., Otorii T., Imai S. Effects of 2-nicotinamidoethyl nitrate on the cardiovascular system. Jpn Heart J. 1979 Nov;20(6):881–895. doi: 10.1536/ihj.20.881. [DOI] [PubMed] [Google Scholar]
  20. Nakayama K., Fan Z., Marumo F., Sawanobori T., Hiraoka M. Action of nicorandil on ATP-sensitive K+ channel in guinea-pig ventricular myocytes. Br J Pharmacol. 1991 Jul;103(3):1641–1648. doi: 10.1111/j.1476-5381.1991.tb09841.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Neichi T., Tomisawa S., Kubodera N., Uchida Y. Enhancement of PGI2 formation by a new vasodilator, 2-nicotinamidoethyl nitrate in the coupled system of platelets and aortic microsomes. Prostaglandins. 1980 Apr;19(4):577–586. doi: 10.1016/s0090-6980(80)80007-4. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Pieper G. M., Gross G. J. Anti-free-radical and neutrophil-modulating properties of the nitrovasodilator, nicorandil. Cardiovasc Drugs Ther. 1992 Jun;6(3):225–232. doi: 10.1007/BF00051143. [DOI] [PubMed] [Google Scholar]
  24. Pieper G. M., Gross G. J. Salutary action of nicorandil, a new antianginal drug, on myocardial metabolism during ischemia and on postischemic function in a canine preparation of brief, repetitive coronary artery occlusions: comparison with isosorbide dinitrate. Circulation. 1987 Oct;76(4):916–928. doi: 10.1161/01.cir.76.4.916. [DOI] [PubMed] [Google Scholar]
  25. Pluta R. Influence of prostacyclin on early morphological changes in the rabbit brain after complete 20-min ischemia. J Neurol Sci. 1985 Oct;70(3):305–316. doi: 10.1016/0022-510x(85)90172-8. [DOI] [PubMed] [Google Scholar]
  26. Shimshak T. M., Preuss K. C., Gross G. J., Brooks H. L., Warltier D. C. Recovery of contractile function in post-ischaemic reperfused myocardium of conscious dogs: influence of nicorandil, a new antianginal agent. Cardiovasc Res. 1986 Aug;20(8):621–626. doi: 10.1093/cvr/20.8.621. [DOI] [PubMed] [Google Scholar]
  27. Siesjö B. K., Agardh C. D., Bengtsson F. Free radicals and brain damage. Cerebrovasc Brain Metab Rev. 1989 Fall;1(3):165–211. [PubMed] [Google Scholar]
  28. 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]

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

RESOURCES