Paradoxic bradycardia (vasodepressor reaction) induced by inferior vena cava occlusion: the role of alpha- and beta-adrenergic receptors and their interaction.
Vasodepressor reactions, characterized by paradoxic bradycardia, were induced in rats when the inferior vena cava was occluded during an infusion of isoproterenol. The effects of alpha-adrenergic receptors and their interaction with beta-adrenergic receptors on the vasodepressor reaction were examined. Inferior vena cava occlusion was performed for 60 s, and the maximum changes in R-R were measured in 44 rats: (i) in control conditions, during phenylephrine (alpha 1-adrenergic agonist), and during a combined infusion of phenylephrine and isoproterenol the R-R shortened significantly (-16.8 +/- 1.4, -24.1 +/- 2.2, and -4.9 +/- 1.2 ms, respectively); (ii) isoproterenol and phentolamine and prazosin (nonselective and selective alpha-adrenergic antagonists) prolonged the R-R paradoxically (+89.2 +/- 9.5, +58.9 +/- 4.1, and +64.4 +/- 10.2 ms, respectively); (iii) atropine and right vagotomy did not affect the phentolamine-induced R-R prolongation (+66.0 +/- 2.4 and +73.8 +/- 13.7 ms, respectively), but it was blocked by left vagotomy (-9.6 +/- 1.1 ms); (iv) propranolol inhibited the prazosin-induced R-R prolongation (-14.3 +/- 2.8 ms,); (v) epinephrine (alpha- and beta-adrenergic agonist) shortened the R-R interval (-9.5 +/- 2.2 ms), but following prazosin, epinephrine induced R-R prolongation (+13.7 +/- 6.0 ms,); (vi) norepinephrine induced R-R prolongation (+21.0 +/- 6.7 ms). It was concluded that (i) paradoxic bradycardia (vasodepressor reaction) dependent on vagal afferents can be induced by reduced venous return in the presence of excess exogenous beta 1-adrenergic stimulation (isoproterenol) or when endogenous alpha-adrenergic tone is antagonized (phentolamine or prazosin); (ii) the reaction can be blocked by alpha 1-adrenergic stimulation; and (iii) epinephrine does not induce paradoxic bradycardia, whereas norepinephrine does, and this may be due to the stronger alpha-stimulating properties of epinephrine.
Waxman
M B
MB
Department of Medicine, University of Toronto, ON, Canada.
Asta
J A
JA
Cameron
D A
DA
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001919:Bradycardia / Q000503:physiopathology*; D004837:Epinephrine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014628:Vagotomy; D014682:Vena Cava, Inferior / Q000502:physiology*
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D001285:Atropine; D007545:Isoproterenol; D011224:Prazosin; D004837:Epinephrine; D010646:Phentolamine