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. 1991 Jun;103(2):1453–1457. doi: 10.1111/j.1476-5381.1991.tb09810.x

Effects of propafenone on 45Ca movements and contractile responses in vascular smooth muscle.

R Carrón 1, F Pérez-Vizcaino 1, E Delpón 1, J Tamargo 1
PMCID: PMC1908362  PMID: 1884101

Abstract

1. In rat isolated aorta the class Ic antiarrhythmic drug, propafenone, dose-dependently inhibited the contractile responses induced by high K (80 mM) and noradrenaline (NA, 10(-5) M), the IC50s being 2.5 +/- 0.7 x 10(-6) M and 8.7 +/- 0.8 x 10(-6) M, respectively. These inhibitory actions were also observed with propafenone added after the induced contractions. 2. Contractile responses induced by addition of Ca to 0 Ca high-K solution were also inhibited by propafenone (IC50 = 2.5 +/- 0.8 x 10(-6) M). Moreover, propafenone inhibited the contractile responses elicited by NA in strips incubated in 0 Ca (IC50 = 1.9 +/- 0.9 x 10(-6) M). 3. Propafenone also inhibited (IC50 = 1.2 +/- 0.4 x 10(-5) M) the development of spontaneous mechanical activity in portal vein segments. 4. Propafenone, 5 x 10(-6) M and 10(-5) M, inhibited 45Ca uptake stimulated by high K or NA without altering 45Ca uptake in resting strips. 5. These results indicated that in rat isolated aortae and portal veins propafenone inhibited Ca entry through voltage-operated channels and NA-induced Ca uptake as well as Ca release from intracellular stores. As a consequence it would reduce the concentration of intracellular free Ca available at the contractile apparatus for vascular smooth muscle contraction.

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Selected References

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  1. Barrigon S., Tejerina T., Delgado C., Tamargo J. Effects of chlorbutol on 45Ca movements and contractile responses of rat aorta and its relevance to the actions of Syntocinon. J Pharm Pharmacol. 1984 Aug;36(8):521–526. doi: 10.1111/j.2042-7158.1984.tb04443.x. [DOI] [PubMed] [Google Scholar]
  2. Barrigón S., Tamargo J. The effect of oxytocin on contractile responses and 45Ca movements in rat isolated aortic strips. Br J Pharmacol. 1986 Apr;87(4):763–770. doi: 10.1111/j.1476-5381.1986.tb14595.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bolton T. B. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev. 1979 Jul;59(3):606–718. doi: 10.1152/physrev.1979.59.3.606. [DOI] [PubMed] [Google Scholar]
  4. Cauvin C., Loutzenhiser R., Van Breemen C. Mechanisms of calcium antagonist-induced vasodilation. Annu Rev Pharmacol Toxicol. 1983;23:373–396. doi: 10.1146/annurev.pa.23.040183.002105. [DOI] [PubMed] [Google Scholar]
  5. Connolly S. J., Kates R. E., Lebsack C. S., Harrison D. C., Winkle R. A. Clinical pharmacology of propafenone. Circulation. 1983 Sep;68(3):589–596. doi: 10.1161/01.cir.68.3.589. [DOI] [PubMed] [Google Scholar]
  6. Delgado C., Tamargo J., Tejerina T. Electrophysiological effects of propafenone in untreated and propafenone-pretreated guinea-pig atrial and ventricular muscle fibres. Br J Pharmacol. 1985 Dec;86(4):765–775. doi: 10.1111/j.1476-5381.1985.tb11098.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Deth R., van Breemen C. Agonist induced release of intracellular Ca2+ in the rabbit aorta. J Membr Biol. 1977 Jan 28;30(4):363–380. doi: 10.1007/BF01869677. [DOI] [PubMed] [Google Scholar]
  8. Deth R., van Breemen C. Relative contributions of Ca2+ influx and cellular Ca2+ release during drug induced activation of the rabbit aorta. Pflugers Arch. 1974 Apr 4;348(1):13–22. doi: 10.1007/BF00587735. [DOI] [PubMed] [Google Scholar]
  9. Dukes I. D., Vaughan Williams E. M. The multiple modes of action of propafenone. Eur Heart J. 1984 Feb;5(2):115–125. doi: 10.1093/oxfordjournals.eurheartj.a061621. [DOI] [PubMed] [Google Scholar]
  10. Ebeigbe A. B., Aloamaka C. P. Mechanism of hydralazine-induced relaxation of arterial smooth muscle. Cardiovasc Res. 1985 Jul;19(7):400–405. doi: 10.1093/cvr/19.7.400. [DOI] [PubMed] [Google Scholar]
  11. Funck-Brentano C., Kroemer H. K., Lee J. T., Roden D. M. Propafenone. N Engl J Med. 1990 Feb 22;322(8):518–525. doi: 10.1056/NEJM199002223220806. [DOI] [PubMed] [Google Scholar]
  12. Godfraind T. Actions of nifedipine on calcium fluxes and contraction in isolated rat arteries. J Pharmacol Exp Ther. 1983 Feb;224(2):443–450. [PubMed] [Google Scholar]
  13. Godfraind T., Kaba A. Blockade or reversal of the contraction induced by calcium and adrenaline in depolarized arterial smooth muscle. Br J Pharmacol. 1969 Jul;36(3):549–560. doi: 10.1111/j.1476-5381.1969.tb08010.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Godfraind T., Miller R., Wibo M. Calcium antagonism and calcium entry blockade. Pharmacol Rev. 1986 Dec;38(4):321–416. [PubMed] [Google Scholar]
  15. Haeusler G. Differential effect of verapamil on excitation-contraction coupling in smooth muscle and on excitation-secretion coupling in adrenergic nerve terminals. J Pharmacol Exp Ther. 1972 Mar;180(3):672–682. [PubMed] [Google Scholar]
  16. Hapke H. J., Prigge E. Zur Pharmakologie von 2'-[2-Hydroxy-3-(propylamino)-propoxy]-3-phenylpropiophenon (Propafenon, SA 79)-hydrochlorid. Arzneimittelforschung. 1976;26(10):1849–1857. [PubMed] [Google Scholar]
  17. Harder D. R., Belardinelli L. Effects of propafenone on TEA-induced action potentials in vascular smooth muscle of canine coronary arteries. Experientia. 1980 Sep 15;36(9):1082–1083. doi: 10.1007/BF01965982. [DOI] [PubMed] [Google Scholar]
  18. Harron D. W., Brogden R. N. Propafenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias. Drugs. 1987 Dec;34(6):617–647. doi: 10.2165/00003495-198734060-00001. [DOI] [PubMed] [Google Scholar]
  19. Hudgins P. M., Weiss G. B. Differential effects of calcium removal upon vascular smooth muscle contraction induced by norepinephrine, histamine and potassium. J Pharmacol Exp Ther. 1968 Jan;159(1):91–97. [PubMed] [Google Scholar]
  20. Karagueuzian H. S., Katoh T., McCullen A., Mandel W. J., Peter T. Electrophysiologic and hemodynamic effects of propafenone, a new antiarrhythmic agent, on the anesthetized, closed-chest dog: comparative study with lidocaine. Am Heart J. 1984 Mar;107(3):418–424. doi: 10.1016/0002-8703(84)90080-2. [DOI] [PubMed] [Google Scholar]
  21. Karaki H., Kubota H., Urakawa N. Mobilization of stored calcium for phasic contraction induced by norepinephrine in rabbit aorta. Eur J Pharmacol. 1979 Jun 15;56(3):237–245. doi: 10.1016/0014-2999(79)90176-6. [DOI] [PubMed] [Google Scholar]
  22. Kohlhardt M. Block of sodium currents by antiarrhythmic agents: analysis of the electrophysiologic effects of propafenone in heart muscle. Am J Cardiol. 1984 Nov 14;54(9):13D–19D. doi: 10.1016/s0002-9149(84)80279-9. [DOI] [PubMed] [Google Scholar]
  23. Kohlhardt M., Seifert C., Hondeghem L. M. Tonic and phasic INa blockade by antiarrhythmics. Different properties of drug binding to fast sodium channels as judged from Vmax studies with propafenone and derivatives in mammalian ventricular myocardium. Pflugers Arch. 1983 Mar 1;396(3):199–209. doi: 10.1007/BF00587856. [DOI] [PubMed] [Google Scholar]
  24. Ledda F., Mantelli L., Manzini S., Amerini S., Mugelli A. Electrophysiological and antiarrhythmic properties of propafenon in isolated cardiac preparations. J Cardiovasc Pharmacol. 1981 Nov-Dec;3(6):1162–1173. doi: 10.1097/00005344-198111000-00002. [DOI] [PubMed] [Google Scholar]
  25. Satoh H., Hashimoto K. Effect of propafenone on the membrane currents of rabbit sino-atrial node cells. Eur J Pharmacol. 1984 Mar 23;99(2-3):185–191. doi: 10.1016/0014-2999(84)90240-1. [DOI] [PubMed] [Google Scholar]
  26. Seipel L., Breithardt G. Propafenone--a new antiarrhythmic drug. Eur Heart J. 1980 Aug;1(4):309–313. doi: 10.1093/oxfordjournals.eurheartj.a061135. [DOI] [PubMed] [Google Scholar]
  27. Sigurdsson S. B., Uvelius B., Johansson B. Relative contribution of superficially bound and extracellular calcium to activation of contraction in isolated rat portal vein. Acta Physiol Scand. 1975 Nov;95(3):263–269. doi: 10.1111/j.1748-1716.1975.tb10050.x. [DOI] [PubMed] [Google Scholar]
  28. Somberg J. C., Tepper D., Landau S. Propafenone: a new antiarrhythmic agent. Am Heart J. 1988 Jun;115(6):1274–1279. doi: 10.1016/0002-8703(88)90021-x. [DOI] [PubMed] [Google Scholar]
  29. Tamargo J., Delgado C. Electrophysiological effects of propafenone on isolated guinea-pig ventricular muscle and sheep Purkinje fibres. Eur J Pharmacol. 1985 Dec 3;118(3):331–340. doi: 10.1016/0014-2999(85)90144-x. [DOI] [PubMed] [Google Scholar]
  30. Tamargo J., Tejerina T. Effects of oxodipine on 45Ca movements and contractile responses in vascular smooth muscle. Br J Pharmacol. 1989 Jun;97(2):339–346. doi: 10.1111/j.1476-5381.1989.tb11959.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Valenzuela C., Delgado C., Tamargo J. Electrophysiological effects of 5-hydroxypropafenone on guinea pig ventricular muscle fibers. J Cardiovasc Pharmacol. 1987 Nov;10(5):523–529. doi: 10.1097/00005344-198711000-00005. [DOI] [PubMed] [Google Scholar]
  32. Valenzuela C., Delpón E., Tamargo J. Electrophysiologic interactions between mexiletine and propafenone in guinea pig papillary muscles. J Cardiovasc Pharmacol. 1989 Sep;14(3):351–357. doi: 10.1097/00005344-198909000-00001. [DOI] [PubMed] [Google Scholar]

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