Paradoxical effect of calcium on some cardiovascular effects of verapamil in the rat

Mari´a C Camilio´n De Hurtado, Oscar A. Gende, Enrique Berduc, Horacio E. Cingolani

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The ability of calcium infusions to reverse some cardiovascular effects of verapamil was tested in anesthetized rats and on isolated rat atria. Intravenous infusions of 1.88 mg/kg verapamil increased the cycle length (CL), lengthened the PR interval (PRi), and decreased the mean arterial pressure (Pa). After these effects were stabilized, a series of infusions of calcium chloride (338 μmol/kg each) were performed. Calcium on the one hand promoted the return of Pa to its basal value; on the other hand, it failed to reverse the effect of verapamil on AV conduction and the first infusion of calcium produced an additional increase in CL of 55 ± 16 ms. This paradoxical effect of calcium was prevented by previous infusion of atropine (0.2 mg/kg). On isolated atria, the increase of calcium concentration in the media ([Ca2+]0) from 1.0 to 6.0 mM increased the concentration frequency by ~40 beats/min, both in atropinized and in nonatropinized preparations. After verapamil, however, the same increase in [Ca2+]0 decreased atrial rate in 50 ± 15 beats/min in nonatropinized atria. The results obtained indicate that extra calcium can overcome the hypotensive effect of verapamil, whereas it paradoxically increases its negative chronotropic effect and fails to reverse its effect on AV conduction. This paradoxical effect of calcium can be prevented, both in vivo and in vitro, by atropine blockade of muscarinic receptors.

Original languageEnglish (US)
Pages (from-to)187-192
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Issue number2
Publication statusPublished - 1987
Externally publishedYes



  • Atrial rate
  • Atropine
  • Calcium
  • Chronotropism
  • Dromotropism
  • Slow channel blocker
  • Verapamil

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

De Hurtado, M. C. C., Gende, O. A., Berduc, E., & Cingolani, H. E. (1987). Paradoxical effect of calcium on some cardiovascular effects of verapamil in the rat. Journal of Cardiovascular Pharmacology, 9(2), 187-192.