Isolated Rabbit Ear Artery Research Articles

Uptake kinetics and ion requirements for extraneuronal uptake of noradrenaline by arterial smooth muscle and collagen.

1. The ionic requirements for noradrenaline uptake into vascular smooth muscle cells were studied by perfusing rabbit isolated ear arteries with noradrenaline (10(-3)M) either in Krebs solution or in Krebs solution modified by altering the concentration of one or more ion. Noradrenaline uptake was measured by quantitative microphotometry.2. Some uptake into smooth muscle continued in isotonic sucrose in the absence of all ions. Omission of Na(+) from the Krebs solution partially inhibited uptake as did high (100 mM) K(+). Omission of K(+), Ca(++) or Mg(++) had no effect on uptake. Lithium was able completely to substitute for Na(+).3. Alteration in ion concentration did not affect the binding of noradrenaline to collagen.4. The kinetics of uptake of noradrenaline into smooth muscle were analysed and found to be saturable with a Km of 4.9 x 10(-4)M.5. It is concluded that the ionic requirements of the transport mechanism for the uptake of noradrenaline by vascular smooth muscle show a relatively low specificity.

Comparison of constrictor responses of the rabbit ear artery to norepinephrine and to sympathetic nerve stimulation.

The perfused isolated rabbit ear artery was used as a vascular model to compare the constrictor responses to exogenous and endogenous norepinephrine. The aim of the study was to estimate the concentrations of norepinephrine reaching the smooth muscle of the artery during sympathetic nerve stimulation. The artery was perfused so that exogenous norepinephrine was introduced exclusively from the adventitial surface; thus, the drug followed a path to the smooth muscle layer similar to that of the endogenous norepinephrine released from the perivascular ring of sympathetic nerves during electrical stimulation of the artery wall. Cocaine was used to remove the influence of neural uptake of norepinephrine on concentrations of the amine reaching the muscle receptor sites. The estimated concentrations of norepinephrine reaching the smooth muscle receptors for each pulse of electrical stimulation ranged from 24.8 ± 5.9 ng/ml (1.47 x 10 -7 M ) to 29.6 ± 7.7 ng/ml (1.75 x 10 -7 M ) over the range of pressure changes from 30 to 100 mm Hg. This finding suggests that the relative sensitivity to endogenous and exogenous norepinephrine is similar at different response levels in this range and that the effect of local factors in the artery on concentrations reaching the smooth muscle is of the same order of magnitude for both endogenous and exogenous norepinephrine.

Biphasic vasoconstriction of the rabbit ear artery.

Sympathetic nerve stimulation and intraluminal norepinephrine infusion for more than 15 seconds produced a biphasic response in the isolated rabbit ear artery perfused with Krebs solution. This response consisted of an initial rapid constriction (phase A), which was followed by partial relaxation, and a final slowly developing constriction (phase B), which lasted for the duration of nerve stimulation or norepinephrine administration. Raising the potassium concentration of the Krebs solution to 12mM decreased the relaxation time between the two constrictor phases in response to norepinephrine; lowering the potassium concentration to 1.2 mM increased the relaxation time and decreased the degree of constriction of both phases. Biphasic vasoconstrictor responses were also elicited by the intraluminal infusion of phenylephrine, histamine, serotonin, or 35 m M potassium. When calcium was absent from the perfusing solution or when manganous sulfate (1m M ) was present, norepinephrine produced only a fast phase A constriction, with no subsequent slow phase B constriction. However, after treatment of the artery with ryanodine, the phase A constriction in response to norepinephrine was markedly inhibited, but the phase B constriction was not. We concluded that the fast phase A constriction depends on the release of calcium from an intracellular pool and that the slow phase B constriction depends on the influx of extracellular calcium.

Effect of acetylcholine on the response of the isolated rabbit ear artery to stimulation of the perivascular sympathetic nerves

In the isolated rabbit ear artery, low concentrations of exogenous acetylcholine inhibited the response of the artery to periarterial electrical stimulation, while much greater concentrations of acetylcholine were required to inhibit the response to exogenous noradrenaline. This action of acetylcholine on periarterial stimulation was suppressed by atropine and potentiated by cholinesterase inhibitors. Neither atropine nor cholinesterase inhibitors, in concentrations which modified the effects of exogenous acetylcholine, altered the response of the artery to periarterial stimulation. The study failed to confirm that either a cholinergic element or endogenous acetylcholine has an effect in the arterial sympathetic nerve response.

Studies on the peripheral pharmacology of fenazoxine, a potential antidepressant drug.

1. The action of fenazoxine, a cyclized analogue of orphenadrine, has been studied on peripheral tissues innervated by adrenergic and cholinergic nerves. The hypothesis that cyclization of the alkyl amino chain of orphenadrine results in a molecule which retains the noradrenaline sensitizing action of orphenadrine but lacks the antimuscarinic activity has been investigated.2. The antimuscarinic activity of fenazoxine, on guinea pig ileum, was approximately 1/30 that of orphenadrine.3. Fenazoxine, desmethylimipramine and cocaine potentiated the response to noradrenaline and sympathetic nerve stimulation on the cat nictitating membrane, isolated rabbit ear artery and isolated driven atrial strip preparations.4. On the driven atrial strip preparation, fenazoxine at concentrations of 5 x 10(-7)M and 1 x 10(-6)M produced a small potentiation of the inotropic response to isoprenaline. At 5 x 10(-6)M and 5 x 10(-5)M fenazoxine antagonized the inotropic response to tyramine.5. Chronic denervation of the cat nictitating membrane abolished the potentiating action of fenazoxine.6. The results presented suggest that fenazoxine inhibits the uptake of catecholamines in a manner similar to that reported for desmethylimipramine and cocaine.7. Evidence is also presented which suggests that fenazoxine, like desmethylimipramine, possesses anti-noradrenaline activity at higher concentrations.

Effect of Monoamine Oxidase Inhibition on the Sensitivity of the Isolated Rabbit Ear Artery to Noradrenaline and to Tyramine.

Australian Journal of Experimental Biology and Medical ScienceVolume 46, Issue 4 p. P-36-P-36 Original Article Effect of Monoamine Oxidase Inhibition on the Sensitivity of the Isolated Rabbit Ear Artery to Noradrenaline and to Tyramine. LB Jellett, LB Jellett Department of Human Physiology and Pharmacology, University of Adelaide, S.A. 5000Search for more papers by this authorIS de la Lande, IS de la Lande Department of Human Physiology and Pharmacology, University of Adelaide, S.A. 5000Search for more papers by this authorJ McNeil, J McNeil Department of Human Physiology and Pharmacology, University of Adelaide, S.A. 5000Search for more papers by this author LB Jellett, LB Jellett Department of Human Physiology and Pharmacology, University of Adelaide, S.A. 5000Search for more papers by this authorIS de la Lande, IS de la Lande Department of Human Physiology and Pharmacology, University of Adelaide, S.A. 5000Search for more papers by this authorJ McNeil, J McNeil Department of Human Physiology and Pharmacology, University of Adelaide, S.A. 5000Search for more papers by this author First published: 01 August 1968 https://doi.org/10.1038/icb.1968.133AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, Issue4August 1968Pages P-36-P-36 Journal of the Australian and New Zealand Society for Immunology RelatedInformation

Effects of some sympathomimetic amines on the response of the rabbit isolated ear artery to noradrenaline and electrical stimulation.

Effects of some sympathomimetic amines on the response of the rabbit isolated ear artery to noradrenaline and electrical stimulation.