Intravenous Injection Of Adrenaline Research Articles

Blood metabolite responses to catecholamine injections in heifers of high or low genetic merit for milkfat production

Abstract Responses to acute intravenous injections of adrenalin and noradrenalin were examined in two groups of heifers (4 heifers/group) differing in predicted genetic merit by a mean of 33 breeding index units. A split-plot design was used in which the heifers were paired, one high breeding index and one low breeding index, for main plot comparisons between breeding index groups. Subplot treatments (four doses: 0, 0.25, 0.5, and 1 µg/kg bodyweight of noradrenalin; and four times of challenge: 1000 hand 1500 h on two consecutive days) were arranged in two 4 × 4 Latin Squares and applied to the four heifer pairs. The design was repeated on Days 3 and 4 using a second catecholamine, adrenalin. The concentrations of glucose and non-esterified fatty acids were measured in plasma collected at intervals (− 15, − 1, 5, 10, 15,20, 30, 45, 60, and 120 min) from treatment. Samples following the highest dose of each catecholamine were also analysed for insulin and 3-hydroxybutyrate. Glucose response to adrenalin in...

Phosphorylation of the glycogen-binding subunit of protein phosphatase-1G by cyclic-AMP-dependent protein kinase promotes translocation of the phosphatase from glycogen to cytosol in rabbit skeletal muscle.

The glycogen-bound form of protein phosphatase-1 (termed protein phosphatase-1G) is composed of the catalytic (C) subunit complexed to a glycogen-binding (G) subunit that anchors the enzyme to glycogen [Strålfors et al. (1985) Eur. J. Biochem. 149, 295-303]. Incubation of purified protein phosphatase-1G with cyclic-AMP-dependent protein kinase and MgATP, which leads to stoichiometric phosphorylation of the G-subunit [Caudwell et al. (1986) FEBS Lett. 194, 85-90], was found to promote the release of the phosphatase from glycogen; similar observations were made using glycogen-protein particle preparations. An intravenous injection of adrenaline decreased protein phosphatase-1 activity associated with the glycogen-protein particles by 50% with a corresponding increase in the amount present in the cytosol. By contrast, adrenaline did not affect the distribution of glycogen synthase or glycogen phosphorylase which remained entirely bound to glycogen in these experiments. The specific release of protein phosphatase-1 from glycogen may facilitate its inactivation by inhibitor-1 in the cytosol, thereby preventing dephosphorylation of the glycogen metabolising enzymes. Translocation of protein phosphatase-1 may represent a novel mechanism for the activation of glycogenolysis and inhibition of glycogen synthesis by adrenaline.

A simple method for the production of ventricular tachycardia in the rat and guinea pig

A simple method for the production of ventricular tachycardia in the rat and guinea pig was developed. The animals were made to inhale benzene vapors for 2 min. An intravenous injection of adrenaline was given during the last 30 sec of benzene administration. Ventricular tachycardia developed in 95% of the animals used. Development of ventricular tachycardia in guinea pigs was earlier than in rats, but the duration of the ventricular tachycardia was almost equal in both species of animals. The arrhythmia developed by this method is of short duration, reliable, and reproducible. This method can be utilized for the rapid screening of antiarrhythmic agents.

Postsynaptic α1- and α2- adrenoceptors mediating the action of the sympathetic system on muscle spindles, in the rabbit

In anaesthetized and curarized rabbits, the cervical sympathetic nerve (CSN) stimulation induces in jaw elevator muscles a tension response which can be mimicked by the intravenous injection of adrenaline, noradrenaline and phenylephrine. This response, previously described and attributed to the contraction of muscle spindle fibres, is entirely mediated by α-adrenoceptors. The administration of phenoxybenzamine (2.5–3.5 mg/kg) markedly inhibits the responses to the sympathetic stimulation and to the injection of adrenergic agonists. Rauwolscine (1 mg/kg) reduces the development of tension induced by both CSN stimulation and noradrenaline injection without significantly affecting the response to phenylephrine. These data suggest the presence of postsynaptic α 1- and α 2-madrenoceptors in intrafusal muscle fibres. Moreover, the possibility that α 2-adrenoceptors may also have an extrasynaptic location is entertained.

Effect of stress on calcium homeostasis in sheep.

The acute effect of stress on the plasma and cerebrospinal fluid (CSF) immunoreactive parathyroid hormone (PTH) response was studied in 6 merino sheep. Stress was exerted by weak periodical electric square waves (PESW). In addition, the effect of intravenous injection of adrenaline was studied. Under stress conditions (PESW or adrenaline injection), plasma PTH increased up to 30% and up to 50%, respectively. Weak periodical electric square waves of 3-4 mA decreased CSF PTH concentrations by up to 50%. The effect of adrenaline injection on the CSF PTH was not significant. Total calcium and magnesium in plasma and CSF did not change. Our results showed that the effect of stress on the CSF PTH is opposite to the effect on plasma PTH, and suggest that both, PESW and adrenaline, affected PTH in plasma and CSF by a Ca-independent mechanism.

Intrinsic and extrinsic mechanisms involved in the cerebrovascular reaction elicited by immobilization stress in rabbits

Variations in cerebral blood flow and partial pressures of oxygen and carbon dioxide (pO 2, pCO 2) were studied in rabbits during short-duration (1 min) immobilization stress. The techniques used enabled us to determine these variables locally in the caudate nucleus in a continuous, simultaneous and quantitative fashion. It could be shown that cerebral blood flow and arterial blood pressure increased in parallel immediately after inducing the stress reaction, and that pO 2 increased further, indicating that cerebral oxygen supply is maintained by the hyperaemia. Previous administration of a β-receptor blocker or of a cholinergic receptor blocker significantly diminished the cerebrovascular reaction to stress, inducing a decrease in pO 2 during the reaction. Administration of both blockers nearly abolished the cerebral vasodilatation studied. Previous administration of an α-receptor blocker enhanced the reactive hyperaemia. No disturbance of the blood-brain barrier could be observed in rabbits subjected to stress. Intravenous injection of adrenaline, as well as angiotensin II inducing similar increases in blood pressure, had no comparable effect on the blood flow. The conclusion is that in this model of anxiety, neurogenic mechanisms are involved in the provision of a sufficient oxygen supply to the brain.

Discharge pattern of afferent fibers from a neuroma

Discharge properties of afferent units from experimentally produced stump neuromata in the superficial peroneal nerve of the cat hind limb were investigated electrophysiologically. The superficial peroneal nerves were cut and ligated 6–245 days before the experiments. Myelinated and chiefly unmyelinated axons were analyzed. The following results were obtained: (1) 3.9 ± 3% (mean ± S.D.) of axons from early neuromata (days 6–27) and 13.4 ± 10.7% of axons from old neuromata (more than 50 days after nerve severance) showed ongoing activity. The rate of ongoing activity was usually below 1 imp/sec (73%) and rarely above 4 imp/sec and its pattern, in most cases, was irregular. Some myelinated afferents had regular or irregular bursting patterns. (2) Mechanical stimulation of the neuroma excited 19.4 ± 9.6% of the axons from young neuromata and 32.8 ± 14.9% of the axons from old neuromata. Part of these mechanosensitive units exhibited pronounced after-discharges. Some 20% of the units which could be excited, probably ephaptically, by stimulation of other afferent fibers in the common peroneal nerve were excited by pressure applied to the neuroma. (3) About 20–40% of the units with ongoing activity (3–5% of all axons) responded weakly to intravenous injections of adrenaline and noradrenaline and to repetitive stimulation of the lumbar sympathetic trunk. (4) Recording from distally cut fiber bundles showed that part of the axons could be activated by electrical stimulation of the nerve distal to the recording site and by mechanical stimulation of the neuroma. Most of these axons were unmyelinated. This result indicates that afferent axons either branch or interact ephaptically a long distance proximal to the neuroma in the neuroma nerve. (5) The results are discussed with respect to similar results obtained on afferent fibers from experimentally produced neuromata of the sciatic nerve of mice and rats.

Rat endometrial bioelectric activity in vivo and in vitro: effects of adrenaline.

The transuterine potential difference (p.d.) generated by the endometrium was measured in vivo in anaesthetized, ovariectomized rats treated with 10 micrograms oestradiol-17 beta each day for 3 days. Intravenous injection of adrenaline induced transient hyperpolarization of the p.d.; sigmoid dose-dependency was observed over the range 2-40 micrograms/kg. Pre-treatment of the rats with syrosingopine shifted the dose-response curve to the left (enhancement) while combined propranolol (800 micrograms/kg) and phentolamine (800 micrograms/kg) shifted the dose-response curve to the right (depression). Isoprenaline gave similar quantitative changes in the p.d. in vivo which displayed a similar time course and sigmoid dose-dependency. Propranolol alone (800 micrograms/kg) shifted this dose-response curve significantly to the right. Addition of adrenaline or isoprenaline to the serosal solution bathing uteri incubated in vitro after removal from oestradiol-treated rats induced changes in endometrial bioelectric activity that exhibited sigmoid dose-response curves for the transuterine p.d. and short-circuit current (Isc). Propranolol significantly shifted the dose-response curves for adrenaline to the right. Only adrenaline caused small but significant decreases in the uterine resistance but these were not dose-dependent. Acetylcholine, 5-hydroxytryptamine, noradrenaline and phenylephrine had no effect on the transuterine p.d. in vivo or in vitro or on the Isc in vitro. No significant electrical changes could be induced by adrenaline or any of the other drugs across the uteri from untreated ovariectomized rats either in vivo or in vitro. The transluminal membrane p.d. of surface endometrial cells measured with micro-electrodes was depolarized by an addition of serosal adrenaline but only 41% of the cells successfully impaled responded in this way. The results indicate that endometrial cells under oestrogen stimulation possess electrogenic processes that can be modulated specifically by adrenaline through the mediation of a serosally sited beta-adrenoceptor. The physiological role of the mechanism has yet to be established.

Changes in spontaneous ureteral peristalsis in experimental shock with and without administration of adrenaline during shock.

In a control group of anaesthetized dogs, a reduction in the number and speed of peristaltic movements of the ureter was observed during anaphylactic and dye shock. In the second, experimental, group of dogs the effect during fully-developed shock of an intravenous injection of adrenaline at the maximum active dose on the ureter dynamics was investigated. It was found that adrenaline increased the number and, to an even greater extent, the speed of peristaltic movements over a period of a few minutes' duration during which the arterial pressure remained high. It seems that adrenaline first and foremost facilitates the conduction of peristaltic stimuli in the ureter.

Physiological evidence for the occurrence of pathways shunting blood away from the secondary lamellae of eel gills.

1. Several cardiovascular and respiratory measurements have been performed in eels before and after intravenous injections of adrenaline. These experiments have allowed a comparison to be made of values for the cardiac output determined directly (Q) and using the Fick principle (QF) on individual fish under these two conditions. 2. Under control conditions it was shown that QF/Q = 0.72, indicating that about 30% of the mixed venous blood afferent to the gills is returned directly to the heart and bypasses the lamellar circulation via veno-venous anastomoses between the afferent filament arteries and the central venous space of the gill filaments. 3. Adrenaline, which during winter only has its action due to stimulation of alpha-adrenoreceptors, induced a hypoventilation but no changes in cardiac output in spite of a bradycardia. The oxygen content of the mixed venous blood was markedly increased whereas Ca,O2 remained unchanged as did the percentage utilization of oxygen from the water as it passed over the gills. The efferent blood flow from the gills after injection of adrenaline was almost equal to the total cardiac output. It is suggested that such a circulatory change was due to adrenaline-mediated constriction of veno-venous anastomoses in the gills of the eel.

Effect of Coccidiosis on Heart Composition and Function in Young Turkeys

Heart composition and function were measured in turkey poults inoculated with Eimeria meleagrimitis or E. adenoeides oocysts. Heart weights of infected poults were significantly lower than those of uninfected controls. Lipid levels of the heart were significantly reduced on day 4 postinoculation (PI) with E. meleagrimitis and on day 6 PI with E. adenoeides. The reduced lipid levels were closely associated with decreases in body weight. The protein per gram of heart tissue increased as the lipid levels decreased. Heart glycogen, when expressed as microgram per milligram of protein, decreased. However, the concentration of glycogen per gram of tissue apparently changed very little. Moisture levels of hearts from infected and control poults did not differ significantly. Heart rates and mean blood pressures of poults infected with E. adenoeides were slightly (approximately 8%) lower than values in control poults. However, exposure to stress in the form of ice baths or intravenous injection of epinephrine caused more severe and prolonged fluctuations in heart rate and blood pressure of the infected poults than in those of the controls.

Experimental central serous chorioretinopathy in monkey eyes: fluorescein angiographic findings.

In an adult Japanese monkey (Macaca fuscatus), intravenous injections of adrenalin were repeated daily: 0.125 mg/kg for 7 days and 0.375 mg/kg from the 11th day on. In a cynomolgus monkey (Macaca irus), daily injections were carried out with intravenous adrenalin (0.11 mg/kg for 12 days and a double dose from the 13th day on) and also with intramuscular prednisolone. After the 39th injection in the former and after the 32nd injection in the latter monkey, disciform serous retinal detachment was seen to occur in the posterior pole region, and fluorescein angiography revealed multiple dye leakage spots at the level of the retinal pigment epithelium. Sometimes these changes subsided, but on continuing injections, these changes recurred on new locations. Two types of fluorescein leakage spots were recognized, i.e. ink blot type with progressive simple enlargement with time and the mushroom or jet type showing these patterns during enlargement. No abnormality was found in the optic disc, retinal vessels or in the choroidal circulation. The fluorescein angiographic findings were in close resemblance with those seen in the human central serous chorioretinopathy. It was discussed that these fundus changes of the monkey eye produced by repeated adrenalin injections would serve as a good animal model of the human disease.

Effect of lithium preparations on the toxic effects of adrenalin

Experiments on rats have shown that intravenous injection of adrenaline in a dose of 0.3-0.4 mg/kg causes cardiac arrhythmia. In this case the primary arrhythmia developing immediately after adrenaline injection is followed by the recovery of sinusal rhythm which was replaced by the secondary arrhythmia. Apart from arrhythmias, there developed pulmonary edema. The animals died 2--3 minutes after adrenaline injections. Lithium chloride and lithium hydroxybutyrate removed the secondary arrhythmia and pulmonary edema. Lithium hydroxybutyrate has proved to be more effective.

Pharmacological Modification of Hypertensive Blood‐Brain Barrier Opening

Abstract: Acute hypertension was induced by intravenous injection of adrenaline (20 μg/kg) or bicuculline (1.2 mg/kg) in conscious, unrestrained rats with indwelling catheters in aorta and a jugular vein. Three min. after the blood pressure increase, the rats were anaesthetized, and the brains perfused in situ for 1 min. to remove blood and tracers from cerebral vessels. Evans blue‐albumin and 125I labelled serum albumin were used as tracers of the blood‐brain barrier function. Pretreatment with trifluoperazine, thioridazine, imidazole and desipramine significantly reduced the leakage of albumin into the brain compared to non‐treated controls. Acute hypertension enhances pinocytosis activity in cerebral vessels. It is argued that the protective effect of the drugs mentioned may be mediated via an inhibition of the formation of pinocytotic vesicles.

Beta 2-adrenoceptors mediate the stimulating effect of adrenaline on active electrogenic Na-K-transport in rat soleus muscle.

The relative role of beta 1- and beta 2-adrenoceptors in mediating the stimulating effect of adrenaline on active electrogenic Na-K-transport has been assessed in experiments on rat soleus muscles in vitro and in vivo. 2 In the rat isolated soleus muscle, adrenaline (10(-6) M) increases the resting membrane potential (EM) by 5.8 mV and stimulates 22Na-efflux and ouabain-suppressible 42K-uptake by 91 and 94%, respectively. 3 All of these effects are completely blocked by propranolol (10(-5) M), whereas the beta 1-selective adrenoceptor antagonist, metoprolol, was found to be at least 50 times less potent. 4 The beta 2-adrenoceptor agonist, salbutamol, was at least 100 times as potent as H133/22 (a beta 1-selective agonist) in stimulating 22Na-efflux and 42K-influx. 5 In experiments performed under pentobarbitone anaesthesia, the intravenous injection of adrenaline (5 microgram) or salbutamol (0.5 to 50 microgram) led to a rapid and marked increase in the EM of the exposed soleus muscle. This hyperpolarizing effect could not be accounted for by the concomitant, relatively modest change in extracellular K.

The Hormonal Control of Glycogen Metabolism

Inhibitor-1 has been shown to be phosphorylated in skeletal muscle in vivo. In normal fed animals the degree of phosphorylation was 31 +/- 7% and this value increases to 70 +/- 12% following an intravenous injection of adrenaline. The results imply that the phosphorylation of inhibitor-1 may be equally as important as the phosphorylation of phosphorylase kinase in elevating the levels of phosphorylase a. The role of inhibitor-1 in metabolism is discussed.

Mechanism of cardiac output response to hypertonic sodium chloride infusion in dogs

Hypertonic sodium chloride and tris(hydroxymethyl)amino-methane (Tris) hydrochloride (0.3 mmol/kg.min) were infused intravenously into chloralose-anesthetized dogs over a 20-min period. Cardiac output, maximum left ventricular dP/dt, and (dP/dt)/P increased by 55, 33, and 23%, respectively, during NaCl infusion, but Tris HCl infusion had no effects. NaCl infusion did not change heart rate or left ventricular end-diastolic pressure. Mean systemic and pulmonry arterial blood pressures increased, whereas total peripheral and pulmonary vascular resistances decreased. Responsiveness of cardiac beta-adrenergic receptors, as determined by serial intravenous injections of epinephrine, was not affected by NaCl infusion. Plasma catecholamine concentration, however, increased during NaCl infusion. In addition, the increases in cardiac output, maximum left ventricular dP/dt and (dP/dt)/P were abolished by prior treatment with practolol, a cardioselective beta-adrenergic receptor blocking agent. These results suggest that the hemodynamic effects of NaCl infusion were caused, at least in part, by the inotropic action of catecholamines.

Prostaglandin E<sub>2</sub> and Epinephrine Participate in Cyclical Reduction of Coronary Blood Pressure and Flow

The effects of the agents that inhibited synthesis of prostaglandins (PGs) and thromboxanes (TXs) on cyclical reduction of blood flow in partially constricted coronary artery of anesthetized dog were examined. The cyclical reduction of coronary blood flow was eliminated by intravenous injections of aspirin that inhibited synthesis of endoperoxides, of benzydamine that inhibited synthesis of endoperoxides and TX A2, and of phenylbutazone that inhibited synthesis of PG E2, but was not of reduced glutathione that inhibited synthesis of TX A2 and accelerated synthesis of PG E2. In the preparations in which cyclical reduction of blood flow did not occur spontaneously, intracoronary injection of PG E2, but not of PG F2a, induced the cyclical reduction. The cyclical reduction was also induced by intravenous injections of epinephrine and reduced glutathione that accelerated synthesis of PG E2. The results indicate participation of PG E2 in the cyclical reduction of coronary blood flow.

Experimental studies on cerebral vasospasm. --Part 1: Evaluation of the electrical activities recorded from the smooth muscles of the basilar artery with vasospasm-- (author's transl)

Since the investigations by Brawley and coworkers it has been known that cerebral vasospasm is a biphasic phenomenon: the acute phase occurs within minutes after the subarachnoid hemorrhage and lasts less than one hour. The chronic phase occurs 3 to 24 hours after the hemorrhage. Numerous workers so far have carried out studies on the vasospasm based on the assumption that the vasospasm is due to functional constriction of the smooth muscles of the cerebral arterial wall. However, it has not been demonstrated whether the vasospasm, not only in the acute phase but also in the chronic phase, is actually a functional spasm of the arterial smooth muscles or not. To investigate such basic problems related to the cerebral vasospasm, we attempted to record and evaluate the electrical activity from the smooth muscles of the arterial wall in vivo which underwent experimentally induced vasospasm. The results thus obtained were as follows. 1. No spontaneous electrical activity was recorded from the intact basilar arteries of normal dogs. From the basilar arteries of the denervated dogs, however, electrical activities, spikes with 100 to 200 msec. duration and less than 1 mV amplitude, were induced by intravenous injection of epinephrine. 2. Similar electrical activities were reocrded during the entire course of the acute phase of vasospasm. The onset of the electrical activity coincided with the onset of vasospasm and they lasted less than 120 minutes. 3. In the chronic phase of vasospasm no electrical activity was recorded from the arteries which definitely showed the phenomenon of so-called vasospasm. Even when epinephrine was administrated to the denervated dogs with the chronic phase of vasospasm, no electrical activity of the arterial wall could be induced. From these experimental results, we concluded that the acute phase of vasospasm is due to functional constriction of the arterial smooth muscles, and that it is not due to functional constriction in the chronic phase but is due to some organic changes of the arterial wall.

Separation of Two Phosphorylase Kinase Phosphatase Activities in Rabbit Skeletal Muscle

The 20-40-fold activation of phosphorylase kinase catalysed by cyclic AMP-dependent protein kinase in the presence of cyclic AMP, ATP and Mg2+ ions in vitro (Walsh et al., 1968) represents one of the events leading to the stimulation of skeletal muscle glycogenolysis by adrenalin. However, recent experiments have demonstrated that this reaction is far more complex than had originally been supposed, and the information which led to this conclusion is summarized below. (1) Phosphorylase kinase was shown to be formed from three types of polypeptide chain, termed a, band y, and the smallest active species of the enzyme had the structure (aby)4. Incubation of phosphorylase kinase with the cyclic AMP-dependent protein kinase and ATP-Mg led to phosphorylation at two unique serine residueslabyunit. The fist mol rapidly entered the /I subunit and paralleled the rise in activity, whereas the second mol was incorporated five times more slowly into the a subunit after a short lag period, without any further effect on activity (Cohen, 1973; Cohen et al., 1975). (2) After phosphorylation of phosphorylase kinase in vitro, the preparation was shown to contain trace endogenous phosphorylase kinase phosphatase activity capable of dephosphorylating both the a and b subunits (Cohen & Antoniw, 1973). (3) The phosphorylation of the a subunit was found to enhance the rate of dephosphorylation of the b subunit and accompanying inactivation of the enzyme by a factor of 50. The results showed that the reversible activation of phosphorylase kinase was associated exclusively with the reversible phosphorylation of the subunit, but that there might also be a novel mechanism for actively regulating the reversal of hormonal activation, associated with the phosphorylation of the a subunit (Cohen & Antoniw, 1973). (4) Intravenous injection of adrenalin was shown to activate phosphorylase kinase 5-10-fold in skeletal muscle in vivo, and was accompanied by phosphorylation of the same two sites on the a and subunits that were labelled in vitro (Yeaman & Cohen, 1974,1975). This showed that the two functional changes associated with the phosphorylation of each site were control mechanisms that operated in vivo. Here we present an extension of these findings and demonstrate that there are in fact two distinct phosphorylase kinase phosphatases in skeletal muscle, one specific for the a subunit, and one specific for the