Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1987 Jun;91(2):411–419. doi: 10.1111/j.1476-5381.1987.tb10296.x

Effects of nipradilol on myocardial ischaemia produced by coronary stenosis in dogs.

K Noguchi, M Sakanashi
PMCID: PMC1853516  PMID: 2886171

Abstract

Effects of nipradilol which is a new beta-adrenoceptor blocking agent endowed with nitroglycerin-like vasodilator actions, its denitrated derivative (denitro nipradilol) and propranolol on abnormalities of regional myocardial shortening produced by partial occlusion of the left circumflex coronary artery (LCX) were studied in anaesthetized open-chest dogs. In the presence of LCX stenosis, nipradilol (0.1 mg kg-1, i.v.) produced marked decreases in heart rate and LVdP/dt without a significant increase in left ventricular end-diastolic pressure (LVEDP). It improved impaired myocardial segment shortening and restored normal cardiac lactate metabolism. Denitro nipradilol (0.2 mg kg-1 i.v.) and propranolol (0.2 mg kg-1 i.v.) both caused similar haemodynamic changes to nipradilol but also produced a significant increase in LVEDP. However, improvement by these two agents of regional dysfunction in the ischaemic myocardium was comparable to those seen with nipradilol. All three agents markedly inhibited isoprenaline-induced tachycardia, but vehicle did not. Atrial pacing abolished the beneficial effect of nipradilol on myocardial shortening in the ischaemic region without affecting other haemodynamic parameters. These results indicate that nipradilol alleviates acute myocardial ischaemia produced by coronary stenosis with similar efficacy to denitro nipradilol and propranolol suggesting, that a major part of the beneficial effect of nipradilol may be attributable to its beta-adrenoceptor blocking action.

Full text

PDF
411

Selected References

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

  1. Abiko Y., Sakai K. Increase of myocardial pH by 1- and d-propranolol during ischemia of the heart in dogs. Eur J Pharmacol. 1980 Jun 27;64(4):239–247. doi: 10.1016/0014-2999(80)90231-9. [DOI] [PubMed] [Google Scholar]
  2. Asada H., Nanjo T., Itoh T., Suzuki H., Kuriyama H. Effects of 3,4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-3-nitroxy-2H-1-bezopyran (K-351) on smooth muscle cells and neuromuscular transmission in guinea-pig vascular tissues. J Pharmacol Exp Ther. 1982 Nov;223(2):560–572. [PubMed] [Google Scholar]
  3. Berdeaux A., Bonhenry C., Duhazé P., Giudicelli J. F., Thuillez C. Influence of heart rate on the effects of prenalterol on regional myocardial blood flow and function during coronary stenosis in dogs. Br J Pharmacol. 1984 Sep;83(1):203–210. doi: 10.1111/j.1476-5381.1984.tb10136.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buck J. D., Gross G. J., Warltier D. C., Jolly S. R., Hardman H. F. Comparative effects of cardioselective versus noncardioselective beta blockade on subendocardial blood flow and contractile function in ischemic myocardium. Am J Cardiol. 1979 Oct;44(4):657–663. doi: 10.1016/0002-9149(79)90284-4. [DOI] [PubMed] [Google Scholar]
  5. Geffin G. A., Drop L. J., Newell J. B., Johnson R. G., O'Keefe D. D., Teplick R. S., Titus J. S., Daggett W. M. Effect of preload on ischaemic and non-ischaemic left ventricular regional function. Cardiovasc Res. 1986 Jun;20(6):415–427. doi: 10.1093/cvr/20.6.415. [DOI] [PubMed] [Google Scholar]
  6. Gross G. J., Lamping K. G., Warltier D. C., Hardman H. F. Effects of three bradycardiac drugs on regional myocardial blood flow and function in areas distal to a total or partial coronary occlusion in dogs. Circulation. 1984 Feb;69(2):391–399. doi: 10.1161/01.cir.69.2.391. [DOI] [PubMed] [Google Scholar]
  7. Kjekshus J. K. Mechanism for flow distribution in normal and ischemic myocardium during increased ventricular preload in the dog. Circ Res. 1973 Nov;33(5):489–499. doi: 10.1161/01.res.33.5.489. [DOI] [PubMed] [Google Scholar]
  8. Kou K., Suzuki H. The effects of 3,4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-3-nitroxy-2H-1-benzopyran (K-351) and its denitrated derivative on smooth muscle cells of the dog coronary artery. Br J Pharmacol. 1983 May;79(1):285–295. doi: 10.1111/j.1476-5381.1983.tb10523.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Nagatomo T., Tsuchihashi H., Sasaki M., Nakagawa Y., Nakahara H., Imai S. Beta-receptor blocking potencies of the three newly synthesized beta-adrenergic antagonists (S-596, K-351, N-696) as assessed with the radioligand binding assay method in rat cardiac muscle membrane treated with neuraminidase. Jpn J Pharmacol. 1984 Feb;34(2):249–254. doi: 10.1254/jjp.34.249. [DOI] [PubMed] [Google Scholar]
  10. Nakaya H., Kimura S., Nakao Y., Kanno M. Effects of nipradilol (K-351) on the electrophysiological properties of canine cardiac tissues: comparison with propranolol and sotalol. Eur J Pharmacol. 1984 Sep 17;104(3-4):335–344. doi: 10.1016/0014-2999(84)90410-2. [DOI] [PubMed] [Google Scholar]
  11. Nanjo T., Kitamura K. Actions of nipradilol (K-351), a new alpha- and beta-adrenoceptor blocker, on the rabbit portal vein. Jpn J Pharmacol. 1984 Aug;35(4):359–369. doi: 10.1254/jjp.35.359. [DOI] [PubMed] [Google Scholar]
  12. Robertson R. M., Wood A. J., Vaughn W. K., Robertson D. Exacerbation of vasotonic angina pectoris by propranolol. Circulation. 1982 Feb;65(2):281–285. doi: 10.1161/01.cir.65.2.281. [DOI] [PubMed] [Google Scholar]
  13. Sakanashi M., Noguchi K., Takeo S., Ito H., Miyamoto Y., Kato T. Effects of nipradilol (K-351) on cardiac function in anesthetized open-chest dogs. Arch Int Pharmacodyn Ther. 1985 Mar;274(1):47–55. [PubMed] [Google Scholar]
  14. Sakanashi M., Takeo S., Ito H., Noguchi K., Miyamato Y., Higa T. Effects of an antihypertensive agent, nipradilol, on isolated coronary artery of the dog. Pharmacology. 1984;29(5):241–246. doi: 10.1159/000138019. [DOI] [PubMed] [Google Scholar]
  15. Schamhardt H. C., Verdouw P. D., Saxena P. R. Improvement of perfusion and function of ischaemic porcine myocardium after reduction of heart rate by alinidine. J Cardiovasc Pharmacol. 1981 Jul-Aug;3(4):728–738. doi: 10.1097/00005344-198107000-00007. [DOI] [PubMed] [Google Scholar]
  16. Theroux P., Franklin D., Ross J., Jr, Kemper W. S. Regional myocardial function during acute coronary artery occlusion and its modification by pharmacologic agents in the dog. Circ Res. 1974 Dec;35(6):896–908. doi: 10.1161/01.res.35.6.896. [DOI] [PubMed] [Google Scholar]
  17. Thuillez C., Berdeaux A., Bonhenry C., Duhaze P., Giudicelli J. F. Effects of propranolol on regional myocardial blood flow and function during severe coronary stenosis in dogs. Eur J Pharmacol. 1983 Sep 2;92(3-4):171–179. doi: 10.1016/0014-2999(83)90284-4. [DOI] [PubMed] [Google Scholar]
  18. Tomoike H., Ross J., Jr, Franklin D., Crozatier B., McKown D., Kemper W. S. Improvement by propranolol of regional myocardial dysfunction and abnormal coronary flow pattern in conscious dogs with coronary narrowing. Am J Cardiol. 1978 Apr;41(4):689–696. doi: 10.1016/0002-9149(78)90819-6. [DOI] [PubMed] [Google Scholar]
  19. Uchida Y. Cardiovascular effect of [3,4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-3-nitrato-2H-1-benzopyran] (K 351). Jpn Heart J. 1982 Nov;23(6):981–988. doi: 10.1536/ihj.23.981. [DOI] [PubMed] [Google Scholar]
  20. Uchida Y., Nakamura M., Shimizu S., Shirasawa Y., Fujii M. Vasoactive and beta-adrenoceptor blocking properties of 3,4-dihydro-8-(2-hydroxy-3-isopropylamino) propoxy-3-nitroxy-2H-1-benzopyran (K-351), a new antihypertensive agent. Arch Int Pharmacodyn Ther. 1983 Mar;262(1):132–149. [PubMed] [Google Scholar]
  21. Vatner S. F. Correlation between acute reductions in myocardial blood flow and function in conscious dogs. Circ Res. 1980 Aug;47(2):201–207. doi: 10.1161/01.res.47.2.201. [DOI] [PubMed] [Google Scholar]
  22. Vatner S. F., Hintze T. H. Mechanism of constriction of large coronary arteries by beta-adrenergic receptor blockade. Circ Res. 1983 Sep;53(3):389–400. doi: 10.1161/01.res.53.3.389. [DOI] [PubMed] [Google Scholar]
  23. Yoshimura M., Kojima J., Ito T., Fujii M., Suzuki J. Pharmacokinetics of nipradilol (K-351), a new antihypertensive agent. II. Influence of the route of administration on bioavailability in dogs. J Pharmacobiodyn. 1985 Jul;8(7):503–512. doi: 10.1248/bpb1978.8.503. [DOI] [PubMed] [Google Scholar]

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

RESOURCES