Mechanisms by which ganglioplegics and atropine enhance cardiovascular responsiveness

Abstract

At least four mechanisms contribute to the increased responsiveness to pressor drugs caused by ganglioplegic agents: 1) Elimination of parasympathetic reflexes alone was found to have a prominent effect on pressor responsiveness, especially to norepinephrine. 2) Elimination of sympathetic compensatory reflexes caused the expected increase in responsiveness. 3) Tetraethylammonium had a direct effect on blood vessels of the dog's perfused hind limb that resulted in sensitization to norepinephrine, though not to angiotensin; this direct effect of the ganglioplegic was similar to that produced by surgical denervation. 4) Tetraethylammonium caused enhancement of response to epinephrine but not to norepinephrine in pithed cats and this effect seems best explained by a blocking action of the ganglioplegic on adrenergic vasodilator receptors. Because of the participation of these different mechanisms, ganglioplegics and surgical denervation do not necessarily affect pressor responsiveness in the same manner. Additionally, the different mechanisms involved account for the various degrees of augmentation of response to different pressor drugs since the latter have their major actions on different portions of the cardiovascular system. Responsiveness may vary greatly during a single experiment and also from day to day; this variability is due in large part to the nervous system since it is abolished by cervical section of the spinal cord.

Effect of autonomic blocking agents on the cardiovascular effects of octapressin in the rat

“…In the unanesthetized dog, an interplay of a spontaneously variable CO and peripheral resistance results in a relatively constant basal BP (Page and Olmsted, 1963). Variability of vascular responsiveness depends mainly on an intact nervous system, since it can be abolished by cervical section of the spinal cord (Page and McCubbin, 1963). It is likely that the use of urethane and pentobarbital anesthesia in our experiments caused considerable inhibition of the central nervous system, and thus may have modified cardiovascular responsiveness.…”

“…Adrenergic blockade caused an increased pressor response to vasopressin as observed by Dekanski (1952), who proposed the use of phenoxybenzaminetreated rats as a sensitive and reliable preparation for the assay of vasopressin. Gardier et al (1965) and Page and McCubbin (1965) described an augmented pressor response to vasopressin following atropine. The phenoxybenzamine-induced increase in the pressor response may be explained in part by the parasympathetic blocking effect of phenoxybenzamine (Romano and Hinshaw, 1965).…”

“…From their experiments, Page and McCubbin (1963) suggested that at least four mechanisms may play a role in the increased pressor response to vasoactive agents following the administration of ganglioplegics to unanesthetized dogs. Elimination of parasympathetic and of sympathetic reflexes, the blocking of ~-vasodilator receptors and a direct sensitizing effect of ganglionic blocking agents on blood vessels.…”

“…To avoid moderator reflexes, which are known to occur in the intact animal (Heymans and Nell, 1958;Page and McCubbin, 1965) and which presumably obscure direct actions on cardiac function (Page and Olmsted, * Present address:: Department of Pharmacology, University of Toronto, Toronto 5, Canada.…”

Augmentation of drug‐induced blood pressure increases in rats by amobarbital

“…As it is well established that ganglion blocking drugs enhance blood pressure responses (Page & McCubbin, 1963), it is possible that amobarbital augments responses to angiotensin and noradrenaline by its ganglion blocking activity (Exley, 1954). Accordingly, blood pressure responses were tested in 9 conscious rats before and after an injection of the ganglion blocking drug, pentolinium (1-0 mg/rat i.v.…”