Mechanisms of Selective CA Antagonist-Induced Vasodilation

  • C. Van Breemen
  • C. Cauvin
  • O. Hwang
  • P. Leyten
  • S. Lukeman
  • K. Meisheri
  • K. Saida
  • H. Yamamoto
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 39)


Vascular smooth muscle is the primary target organ for Ca antagonist (CAt) therapy. It is now well established that CAts bind to and block excitable channels in the cell membrane (1). The question which remains to be answered is why are these agents selective for certain blood vessels and certain modes of activation.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Fleckenstein A: Calcium antagonism in heart and smooth muscle. John Wiley and Sons, 1983.Google Scholar
  2. 2.
    van Breemen C, Hwang 0, Meisheri KD: The mechanism of inhibitory action of diltiazem on vascular smooth muscle contractility. J Pharmacol Exp Ther (218): 459–464, 1981.PubMedGoogle Scholar
  3. 3.
    Aaronson P, vaii Breemen C: Effects of Na gradient manipulation upon cellular Ca, 45 fluxes, and cellular Na in the guinea pig taenia coli. J Physiol (319): 443–461, 1981.PubMedCentralPubMedGoogle Scholar
  4. 4.
    van Nueten JM, Vanhoutte PM: Selectivity of calcium antagonists and serotonin antagonism with respect to venous and arterial tissues. Angiology (32): 476–484, 1981.PubMedCrossRefGoogle Scholar
  5. 5.
    Droogmans G, Raeymaekers L, Casteels R: Electro and pharmacomech-anical coupling in the smooth muscle cells of rabbit ear artery. J Gen Physiol (70): 129: 48, 1977.Google Scholar
  6. 6.
    Saida K, van Breemen C: Mechanism of Ca2+ antagonist induced vasodilation; intracellular actions. Circ Res 52: 137–142, 1983.PubMedCrossRefGoogle Scholar
  7. 7.
    Edman KAP, Schild MO: The need for calcium in the contractile responses induced by acetylcholine and potassium in the rat uterus. J Physiol (161): 424–441, 1962.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Su C, Bevan JA, Ursillo RC: Electrical quiescence of pulmonary artery smooth muscle during sympathomi stimulation. Circ Res (15): 20–27, 1964.CrossRefGoogle Scholar
  9. 9.
    Droogmans G, Raeymaekers L, Casteels R: Electro and pharmacomechanical coupling in the smooth muscle cells of rabbit ear artery. J Gen Physiol (70): 129–148, 1977.PubMedCrossRefGoogle Scholar
  10. 10.
    Somylo AP, Somylo AV: Vascular smooth muscle I, normal structure, Pathology, Biochemistry and Biophysics, Pharmacological Rev 20: 197–272, 1968.Google Scholar
  11. 11.
    Cauvin C, Loutzenhiser R, van Breemen C:: Mechanisms of calcium antagonist induced vasodilation. Ann Rev Pharmacol Toxicol 23:373–396, 1983.CrossRefGoogle Scholar
  12. 12.
    Hermsmeyer K, Trapani A, Abel PW: Membrane potential-dependent tension in vascular smooth muscle. In: Vanhoutte P, Leusen I(eds)Vaodilation. Raven Press, New York, 1981, pp 273–284.Google Scholar
  13. 13.
    Bolton TB: Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev (3): 606–718, 1979.Google Scholar
  14. 14.
    van Breemen C, Aaronson P, Loutzenhiser R: Na Ca interactions in mammalian smooth muscle. Pharmacol Rev (30): 167–208, 1979.Google Scholar
  15. 15.
    Meisheri KD, Hwang O, van Breemen C: Evidenced for two separate Ca2+ pathways in smooth muscle plasmalemma. J Membrane Biol (59):19–25, 1981.CrossRefGoogle Scholar
  16. 16.
    Kazda S, Garthoff B, Meyer H, Schlossman K, Stoepel K: Pharmacology of a new calcium antagonistic compound, isobutylmethyl, 4 dihydro 2, dimethyl (2 nitrophenyl 1) 3, 5 pyridinedicarboxylate (nisoldipine, Bay K5552). Arzneimittelforsch (30): 214–262, 1980 ).Google Scholar
  17. 17.
    Schramm M, Thomas G, Towart R, Frackowisali G: Novel dihydropyridines with positive isotropic action through activation of Ca+ channels. Nature (303): 535–537, 1983.PubMedCrossRefGoogle Scholar
  18. 18.
    Deth R, Casteels R: A study of released Ca fractions in smooth muscle cells of the rabbit aorta. J Gen Physiol (69): 401–416, 1977.PubMedCrossRefGoogle Scholar
  19. 19.
    van Breemen C: Ca requirement for activation of intact aortic smooth muscle. J Physiol (272): 317–329, 1977.PubMedCentralPubMedGoogle Scholar
  20. 20.
    Devine CE, Somlyo AV, Somlyo AP: Sarcoplasmic reticulum and excitation-contraction coupling in mammalian smooth muscle. J Cell Biol (52): 690–718, 1972.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Saida K, van Breemen C: A possible Ca induced Ca release mechanism mediated by norepinephrine in vascular smooth muscle. Pflugers Arch (397): 166–167, 1983.PubMedCrossRefGoogle Scholar
  22. 22.
    Triggle DJ: Biochemical pharmacology of calcium blockers. IN: Calcium Blockers: Mechanisms of Action and Clinical Applications, S. Flaim and R. Zelis eds., Urban and Schwarzenberg, Baltimore, 1932, pp. 121–134.Google Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1984

Authors and Affiliations

  • C. Van Breemen
  • C. Cauvin
  • O. Hwang
  • P. Leyten
  • S. Lukeman
  • K. Meisheri
  • K. Saida
  • H. Yamamoto

There are no affiliations available

Personalised recommendations