Advertisement

Cardiovascular Drugs and Therapy

, Volume 5, Issue 1, pp 131–138 | Cite as

Coronary effects of nicorandil in comparison with nitroglycerin in chronic conscious dogs

  • Kenji Hashimoto
  • Masahiko Kinoshita
  • Yasunori Ohbayashi
Experimental Pharmacology

Summary

The effects of nicorandil (0.2 mg/kg, IV) and nitroglycerin (15 μg/kg, IV) on large and small coronary arteries were compared in conscious dogs instrumented with ultrasonic crystals and electromagnetic flow meters in the circumflex coronary artery. Nicorandil dilated the large coronary arteries to the same extent, but with a longer duration of action than nitroglycerin. The small coronary arteries dilated for a very short period of time with nitroglycerin, but dilated markedly with nicorandil. The dilatory action of nicorandil on large coronary arteries persisted after the action on the small coronary artery fell to the control value, indicating that the dilatory action on the large coronary arteries is due to the direct relaxing effect on smooth muscle and is not the result of the flow-dependent effect. The measurement of the plasma concentration of nicorandil after incremental infusions of the agent showed that the dilation of the small coronary artery took place at only a very high level (above 200 ng/ml). On the other hand, the large coronary arteries responded to nicorandil at a much lower concentration (about 100 ng/ml, the clinically effective plasma concentration of nicorandil) than the small coronary resistance arteries. In conclusion, whereas nicorandil possesses a dilatory action on both large and small coronary arteries, din a clinical setting, with a daily dosage of 15–30 mg, part of the beneficial effects of nicorandil may be the result of a dilation of the large coronary arteries and may be due to the fact that a coronary steal phenomenon does not occur after nicorandil administration.

Key Words

nicorandil nitroglycerin coronary artery diameter coronary blood flow conscious dogs 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Uchida Y, Yoshimoto N, Murao S. Effect of 2-nicotinamidethyl nitrate (SG 75) on coronary circulation.Jpn Heart J 1977;19:112–124.Google Scholar
  2. 2.
    Uchida Y, Yoshimoto N, Murao S. Effects of antianginal agents on cyclical reductions of coronary blood flow.Jpn Heart J 1978;19:904–912.PubMedGoogle Scholar
  3. 3.
    Taira N, Satoh K, Yanagisawa T, et al. Pharmacological profile of a new coronary vasodilator drug, 2-nicotinamidethyl nitrate (SG 75).Clin Exp Pharmacol Physiol 1979;6:301–316.PubMedCrossRefGoogle Scholar
  4. 4.
    Taira N. Similarity and dissimilarity in the mode and mechanism of action between nicorandil and classical nitrate: An overview.J Cardiovasc Pharmacol 1987;10:s1-s9.PubMedCrossRefGoogle Scholar
  5. 5.
    Holzman S. Cyclic GMP as possible mediator of coronary arterial relaxation by nicorandil (SG-75).J Cardiovasc Pharmacol 1983;5:364–370.CrossRefGoogle Scholar
  6. 6.
    Endoh M, Taira N. Relationship between relaxation and cyclic GMP formation caused by nicorandil in canine mesenteric artery.Naunyn Schmiedebergs Arch Pharmacol 1983;322:319–321.PubMedCrossRefGoogle Scholar
  7. 7.
    Endoh M, Iijima T. Effects of nicorandil and its interaction with isoproterenol on force of contraction cyclic nucleotide levels of canine atrial muscle: Comparison with carbachol.J Cardiovasc Pharmacol 1983;5:878–882.PubMedCrossRefGoogle Scholar
  8. 8.
    Yanagisawa T, Taira N. Circumstantial evidence for increased potassium conductance of membrane of cardiac muscle by 2-nicotinamidethyl nitrate (SG-75).Jpn J Pharmacol 1979;29:687–694.PubMedCrossRefGoogle Scholar
  9. 9.
    Yanagisawa T, Taira N. Effect of 2-nicotinamidethyl nitrate (SG-75) on the membrane potential of left arterial muscle fibers of the dog. Increase in potassium conductance.Naunyn Schmiedebergs Arch Pharmacol 1980;312:69–76.PubMedCrossRefGoogle Scholar
  10. 10.
    Yanagisawa T, Taira N. Effects of 2-nicotinamidethyl nitrate (SG-75) on membrane potentials of canine Purkinje fibers:Jpn J Pharmacol 1981;31:409–417.PubMedCrossRefGoogle Scholar
  11. 11.
    Imanishi S, Arita M. Effects of SG-75 (nicorandil) on electrical activity of canine cardiac Purkinje fibers: Possible increase in potassium conductance.J Pharmacol Exp Ther 1983;225:198–205.PubMedGoogle Scholar
  12. 12.
    Furukawa K, Itoh T, Kajiwara M, et al. Vasodilating actions of 2-nicotinamidethyl nitrate on porcine and guinea-pig coronary arteries.J Pharmacol Exp Ther 1981;218:248–259.PubMedGoogle Scholar
  13. 13.
    Itoh T, Kuriyama H. Effects of 2-nicotinamidethyl nitrate on smooth muscle cells and adrenergic transmission in the guinea-pig and porcine mesenteric arteries.J Pharmacol Exp Ther 1981;218:260–270.PubMedGoogle Scholar
  14. 14.
    Karashima T, Itoh T, Kuriyama H. Effects of 2-nicotinamidethyl nitrate on smooth muscle cells of the guinea-pig mesenteric and portal veins.J Pharmacol Exp Ther 1982; 221:472–480.PubMedGoogle Scholar
  15. 15.
    Inoue T, Kuriyama H. Effects of 2-nicotinamidethyl nitrate (nicorandil;SG-75) and its derivatives on smooth muscle cells of the canine mesenteric artery.J Pharmacol Exp Ther 1984;229:793–802.PubMedGoogle Scholar
  16. 16.
    Taira N. Nicorandil as a hybrid between nitrates and potassium channel activators.Am J Cardiol 1989;63:18J-24J.PubMedCrossRefGoogle Scholar
  17. 17.
    Firshman WH. Pharmacology of the nitrates in angina pectoris.Am J Cardiol 1985;56:81.CrossRefGoogle Scholar
  18. 18.
    Camm AJ, Maltz MB. A controlled single-dose study of the efficacy, dose response and duration of action of nicorandil in angina pectoris.Am J Cardiol 1989;63:61J-65J.PubMedCrossRefGoogle Scholar
  19. 19.
    Meany TB, Richardson P. Exercise capacity after single and twice-daily doses of nicorandil in chronic stable angina pectoris.Am J Cardiol 1989;63:66J-70J.PubMedCrossRefGoogle Scholar
  20. 20.
    Kinoshita M, Hashimoto K, Ohbayashi Y. Comparison of antianginal activity of nicorandil, propranolol and diltiazem with reference to the antianginal mechanism.Am J Cardiol 1989;63:71J-74J.PubMedCrossRefGoogle Scholar
  21. 21.
    Kinoshita M, Nishikawa S, Kawakita S. Comparative efficacy of high-dose versus low-dose nicorandil therapy for chronic stable angina pectoris.Am J Cardiol 1986;58:733–738.PubMedCrossRefGoogle Scholar
  22. 22.
    Thormann J, Schlepper M, Kinder M. Effectiveness of nicorandil (SG-75), a new long-acting drug with nitroglycerin effects, in patients with coronary artery disease: Improved left ventricular function and regional wall motion and abolition of pacing-induced angina.J Cardiovasc Pharmacol 1983;5:371–377.PubMedCrossRefGoogle Scholar
  23. 23.
    Kambara H, Nakamura Y, Kawai C. Beneficial effects of nicorandil on cardiovascular hemodynamics and left ventricular function.J Cardiovasc Pharmacol 1987;10(Suppl. 8): s104-s108.PubMedGoogle Scholar
  24. 24.
    Kobayashi K, Hakuta T. Effects of nicorandil on coronary hemodynamics in ischemic heart disease: Comparison with nitroglycerin, nifedipine, and propranolol.J Cardiovasc Pharmacol 1987;10(Suppl. 8):s109-s115.PubMedGoogle Scholar
  25. 25.
    Aizawa T, Ogasawara K, Kato K. Effects of nicorandil on coronary circulation in patients with ischemic heart disease: Comparison with nitroglycerin.J Cardiovasc Pharmacol 1987;10(Suppl. 8):s123-s129.PubMedGoogle Scholar
  26. 26.
    Goodman CC, Castellana FS. A digital sonomicrometer for two-point length and velocity measurements.Am J Physiol 1982;243:H634–639.PubMedGoogle Scholar
  27. 27.
    Yamada A, Tomoike H, Nakamura M, et al. Effect of nicorandil on large epicardial coronary artery in conscious dogs.Arznein-Forsch/Drug Res 1987;11:1252–1255.Google Scholar
  28. 28.
    Kamiyama H, Hinohara Y, Nakano H, et al. Metabolism of N-(2-hydroxyethyl) nicotinamide nitrate (SG-75X4). Pharmacokinetic studies in rats and dogs.Appl Pharmacol 1982;23:261–266.Google Scholar
  29. 29.
    Ishizaki T, Chiba K, Suganuma T, Sakai T, et al. Pharmacokinetics of nicorandil, a new coronary vasodilator, in dogs.J Pharm Sci 1984;73:494–498.PubMedCrossRefGoogle Scholar
  30. 30.
    Suryapranata H, Serruys PW, Hugenholts PG. Coronary vasodilatory action after a single dose of nicorandil.Am J Cardiol 1988;61:292–297.PubMedCrossRefGoogle Scholar
  31. 31.
    Suryapranata H, Serruys PW. Coronary vasodilatory action after nicorandil: A quantitative angiographie study.Am J Cardiol 1989;63:80J-85J.PubMedCrossRefGoogle Scholar
  32. 32.
    Kinoshita M, Hashimoto K, Ohbayashi Y, et al. Differential response of large and small coronary arteries to various agents in conscious dogs.Automedica 9:212, 1987.Google Scholar
  33. 33.
    Sakai K, Ohba Y, Kamiyama H, et al. Pharmacodynamic and metabolism studies on a new coronary vasodilator, n-(2-hydroxyethyl) nicotinamide nitrate (SG-75).Jpn J Pharmacol 1980;30:881–890.PubMedCrossRefGoogle Scholar
  34. 34.
    Nabata H, Sakai K. Effect of a new antianginal agent, nicorandil, on normoxic and anoxic contractions in isolated miniature pig coronary arteries exposed to 5-hydroxytryptamine and norepinephrine: Comparison with nitroglycerin and diltiazem.Eur J Pharmacol 1983;96:37–44.PubMedCrossRefGoogle Scholar
  35. 35.
    Shibata S, Satake N, Takagi T, et al. Relaxing effect of nicorandil (n-2-(hydroxyethyl)-nicotinamide), a new antiangina agent, on the isolated vascular smooth muscle.Eur J Pharmacol 1984;99:219–226.PubMedCrossRefGoogle Scholar
  36. 36.
    Hester RK. Effect of 2-nicotinamidethylnitrate on agonist-sensitive Ca++ release and Ca++ entry in rabbit aorta.J Pharmacol Exp Ther 1985;233:100–111.PubMedGoogle Scholar
  37. 37.
    Imai S, Nakazawa M, et al. Effect of nicorandil on the conductive coronary artery of the dog.J Cardiovasc Pharmacol 1987;10:s10-s16.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1991

Authors and Affiliations

  • Kenji Hashimoto
    • 1
  • Masahiko Kinoshita
    • 1
  • Yasunori Ohbayashi
    • 1
  1. 1.The First Department of Internal MedicineShiga University of Medical ScienceShiga PrefectureJapan

Personalised recommendations