title: Verapamil blockade of the paradoxic bradycardia in rats induced by inferior vena cava occlusion during the administration of isoproterenol or calcium: the role of Ca2+.
abstract: It has been postulated that the vasodepressor reaction results from a vigorous ventricular contraction in the face of a reduced cardiac volume. Paradoxic bradycardia is a major manifestation of vasodepressor reactions. Allowing for the possible extrapolation between paradoxic bradycardia in rats and vasodepressor reactions, we examined calcium's role, an essential component of cardiac contraction, in the paradoxic bradycardia reaction. Paradoxic bradycardia was induced in rats by inferior vena cava occlusion during an isoproterenol infusion, and we examined calcium's role by studying whether verapamil inhibits and CaCl2 causes paradoxic bradycardia, respectively. The maximum changes in R-R were measured during 60 s of inferior vena cava occlusion under the following conditions: (i) in control, the rate accelerated (R-R-21.8 +/- 2.4 ms (mean +/- SE), p < 0.001); (ii) during isoproterenol, paradoxic bradycardia occurred (R-R 98.0 +/- 8.1 ms, p < 0.001), and this was inhibited by verapamil (R-R 5.0 +/- 2.1 ms, p > 0.05) and restored by CaCl2 (R-R 109.3 +/- 6.5 ms, p < 0.001); (iii) during CaCl2 (without isoproterenol), paradoxic bradycardia also occurred (R-R 82.1 +/- 22.9 ms, p < 0.001), and this was also inhibited by verapamil (R-R -18.5 +/- 4.7 ms, p < 0.001). We conclude that verapamil inhibits the inferior vena cava occlusion induced paradoxic bradycardia caused by either isoproterenol or calcium, and these findings support the concept that increased cardiac contractile force triggers a vasodepressor reaction.
authors.affiliation: Department of Medicine, University of Toronto, ON, Canada.
authors.forename: M B
authors.initials: MB
authors.lastname: Waxman
authors.forename: J A
authors.initials: JA
authors.lastname: Asta
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000503:physiopathology / Q000517:prevention & control*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014682:Vena Cava, Inferior / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D014700:Verapamil; D007545:Isoproterenol; D002118:Calcium