Cardiovascular Drugs and Therapy

, Volume 10, Issue 5, pp 581–586 | Cite as

Contrasting effects of betaxolol and propranolol on Ca2+-activated contractions in skinned fibers from canine coronary arteries and ventricular muscles

  • Yoshimi Kitada
Beta Blockers and Calcium
Received:
Accepted:

Summary

The effects of some beta-adrenoceptor antagonists (atenolol, betaxolol, bunitrolol, labetalol, pindolol, and propranolol) on Ca2+ (pCa 5.8)-activated tension development in chemically skinned fibers from canine coronary artery and right ventricular trabeculae were studied. In skinned coronary arteries, Ca2+-activated tension development was decreased by betaxolol and propranolol at concentrations of more than 10−5 and 10−4 M, respectively. The pCa-tension relationships were shifted to the right and down by betaxolol. In contrast, in skinned cardiac muscle Ca2+-activated tension development was increased by betaxolol and propranolol at the same range of concentrations as in coronary arteries, with no change in maximum tension. The pCa-tension relation was shifted to the left by betaxolol. Other beta-adrenoceptor antagonists (atenolol, bunitrolol, labetalol, and pindolol) had no effect on Ca2+-induced contraction in either muscle type. These results indicate that among beta-adrenoceptor antagonists, only betaxolol and propranolol can directly modulate the Ca2+ sensitivity of myofilaments and have opposite effects on the contractile system in canine cardiac and vascular smooth muscle.

Key Words

betaxolol propranolol Ca2+ sensitivity cardiac muscle smooth muscle skinned fibers contractile protein 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Spedding M.. Direct inhibitory effects of some ‘calcium-antagonists’ and trifluoperazine on the contractile proteins in smooth musclé. Br J Pharmacol 1983;79:225–231.Google Scholar
  2. 2.
    Itoh H, Ishikawa T, Hidaka H. Effects on calmodulin of bepridil, an antianginal agents. J Pharmacol Exp Ther 1984;230:737–741.Google Scholar
  3. 3.
    Solaro RJ, Bousquet P, Johnson JD. Stimulation of cardiac myofilament force, ATPase activity and troponin C Ca++ binding by bepridil. J Pharmacol Exp Ther 1986;238: 502–507.Google Scholar
  4. 4.
    Duval N, Lee CR, Econ MT, Pertruzzo P, Langer SZ. The β1-adrenoceptor antagonist, betaxolol, is not released from the heart of the anesthetized dog during sympathetic nerve. Br J Pharmacol 1989;95:683–688.Google Scholar
  5. 5.
    Cavero I, Leferver-Borg F, Manoury P, Roach AG. In vitro and in vivo pharmacological evaluation of betaxolol, a new potent, and selective β1-adrenoceptor antagonist. In: Morselli RL, ed. Betaxolol and Other Beta-Adrenoceptor Antagonists. L.E.R.S. New York: Raven Press, 1983:31–42.Google Scholar
  6. 6.
    Bessho H, Suzuki J, Tobe A. Vascular effects of betaxolol, a cardioselective β-adrenoceptor antagonist, in isolated rat arteries. Jpn J Pharmacol 1991;55:351–358.Google Scholar
  7. 7.
    Satoh N, Suzuki J, Bessho H, et al. Effects of betaxolol on cardiohemodynamics and coronary circulation in anesthetized dogs: Comparison with atenolol and propranolol. Jpn J Pharmacol 1990;54:113–119.Google Scholar
  8. 8.
    Endo M, Kitazawa T. E-C coupling studies on skinned cardiac fibers. In: Morad M, ed. Biophysical Aspects of Cardiac Muscle. New York: Academic Press, 1978:307–327.Google Scholar
  9. 9.
    Kitada Y, Narimatsu A, Matsumura N, Endo M. Contractile proteins: Possible targets for MCI-154, a novel cardiotonic agent. Eur J Pharmacol 1987;134:229–231.Google Scholar
  10. 10.
    Iino M. Tension response of chemically skinned fibre bundles of the guinea pig taenia caeci under varied ionic environments. J Physiol 1981;320:449–467.Google Scholar
  11. 11.
    Fabiato A, Fabiato F. Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J Physiol (Paris) 1979;75:463–505.Google Scholar
  12. 12.
    Bessho H, Suzuki J, Kitada Y, Narimatsu A, Tobe A. Antihypertensive effects of betaxolol, a cardioselective β-adrenoceptor antagonist, in experimental hypertensive animals. Jpn J Pharmacol 1990;50:315.Google Scholar
  13. 13.
    Dage RC, Hsieh CP, Spedding M. Vasodilation by medroxalol mediated by β2-adrenergic receptor stimulation. J Cardiovasc Pharmacol 1983;5:143–150.Google Scholar
  14. 14.
    Barrett AM. Therapeutic applications of β-adrenoceptor antagonists. In: Morselli PL, Kilborn JR, Cavero I, Harrison DC, Langer SZ, eds Betaxolol and Other β1-Adrenoceptor Antagonists. L.E.R.S. Monograph Series, Vol. 1. New York: Raven Press, 1983:68–69.Google Scholar
  15. 15.
    Lues I, Siegel R, Harting J. Effect of isomazole on the responsiveness to calcium of the contractile elements in skinned cardiac muscle fibers of various species. Eur J Pharmacol 1988;146:145–153.Google Scholar
  16. 16.
    Edes I, Kiss E, Kitada Y, Powers FM, Papp JG, Kranias EG, Solaro RJ. Effects of levosimendan, a cardiotonic agent targeted to troponin C, on cardiac function and on phosphorylation and Ca2+ sensitivity of cardiac myofibrils and sarcoplasmic reticulum in guinea pig heart. Circ Res 1995;77: 107–113.Google Scholar
  17. 17.
    Su JY, Malencik DA. Effects of (+)-propranolol on intracellular mechanisms of contraction in striated muscle of the rabbit. Naunyn Schmiedbergs Arch Pharmacol 1985;331: 194–201.Google Scholar
  18. 18.
    Chatterjee K. Potential use of third-generation β-blockers in heart failure. J Cardiovasc Pharmacol 1989;14(Suppl): S22-S27.Google Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Yoshimi Kitada
    • 1
  1. 1.Pharmaceutical Laboratory I, Yokohama Research CenterMitsubishi Chemical CorporationYokohamaJapan

Personalised recommendations