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L Hedler

Publications and source records attributed to L Hedler.

At least 19 recordsLinked to original sources
PubMed1990

Peripheral presynaptic facilitatory effect of angiotensin II on noradrenaline release in anesthetized rabbits.

The function of presynaptic angiotensin II receptors at postganglionic sympathetic terminal axons under conditions of uninterrupted sympathetic impulse traffic was studied in anesthetized rabbits (alfadolone + alfaxalone). Mean arterial pressure, postganglionic renal sympathetic firing rate, the arterial plasma noradrenaline concentration, and heart rate were measured before (basal values) and at the end of 4-min infusions of sodium nitroprusside. Angiotensin II (20 or 100 ng kg-1 min-1) caused dose-dependent increases of basal mean arterial pressure and decreases of basal sympathetic nerve activity and heart rate, but did not change the basal plasma noradrenaline concentration. Moreover, it shifted the sympathetic nerve activity-plasma noradrenaline relationship in a manner indicating an increase of the average release of noradrenaline per action potential. Angiotensin II at 100 ng kg-1 min-1 had an additional effect, at any given blood pressure, sympathetic nerve activity and heart rate were lower than in the controls. Captopril (1 mg kg-1 followed by 1 mg kg-1 h-1) caused no change in any parameter. The results demonstrate that exogenous angiotensin II activates release-facilitating receptors at postganglionic sympathetic neurons in rabbits with ongoing sympathetic nerve activity. Endogenous angiotensin II, however, played no role in cardiovascular regulation under the present, acute experimental conditions. Vasopressin, which was studied for comparison, lacked a presynaptic effect on the release of noradrenaline but caused sympathoinhibition by an action on a central component of the baroreflex.

Anesthesia↗
PubMed1989

Peripheral presynaptic and central effects of clonidine, yohimbine and rauwolscine on the sympathetic nervous system in rabbits.

The function of presynaptic alpha 2-autoreceptors at postganglionic sympathetic neurones under conditions of normal, ongoing sympathetic impulse traffic was studied in anaesthetized rabbits (alfadolone + alfaxalone). Clonidine was used as an alpha 2-adrenoceptor agonist, and yohimbine and rauwolscine were used as antagonists. Mean arterial pressure, postganglionic renal sympathetic firing rate, arterial plasma noradrenaline concentration and heart rate were measured before (basal values) and at the end of 3-min infusions of sodium nitroprusside and phenylephrine, which were given to modulate efferent activity in the sympathetic nervous system through the baroreflex. The nitroprusside- and phenylephrine-induced changes of mean arterial pressure produced the expected changes in sympathetic nerve activity, plasma noradrenaline and heart rate. Clonidine (5 micrograms kg-1 + 0.5 micrograms kg-1 min-1) reduced the basal mean arterial pressure, sympathetic nerve activity and heart rate. It also reduced the nitroprusside-induced increase in the plasma noradrenaline level without changing the nitroprusside-induced increase in sympathetic firing. These results, as well as the mean arterial pressure-sympathetic nerve activity and the sympathetic nerve activity-plasma noradrenaline function curves indicate that clonidine inhibited both sympathetic tone centrally and the average release of noradrenaline per action potential peripherally. Yohimbine (1 mg kg-1 + 0.1 mg kg-1 h-1) and rauwolscine (0.5 mg kg-1 + 0.1 mg kg-1 h-1) increased the basal plasma noradrenaline level without any increase of renal sympathetic nerve activity. They also enhanced the nitroprusside-induced increase in plasma noradrenaline without any enhancement of the nitroprusside-induced increase in sympathetic firing. The hypotensive response to nitroprusside was attenuated, whereas the heart rate response was augmented. These results, as well as the mean arterial pressure-sympathetic nerve activity and the sympathetic nerve activity-plasma noradrenaline function curves indicate that the main effect of yohimbine and rauwolscine was to increase the average release of noradrenaline per action potential. The simultaneous measurement of postganglionic sympathetic nerve activity and the arterial plasma noradrenaline concentration proved suitable to differentiate central (or ganglionic; this distinction was not possible) effects of alpha 2-adrenoceptor ligands from peripheral presynaptic effects. The results show that endogenous presynaptic, alpha 2-adrenergic autoinhibition of noradrenaline release from postganglionic sympathetic neurones operates physiologically in anaesthetized rabbits with ongoing, uninterrupted sympathetic nerve activity. The results also indicate that blockade of alpha 2-autoreceptors enhances the sympathetic reflex compensatory response to a hypotensive stimulus.

Animals↗
PubMed1989

Facilitation of the release of noradrenaline: an extra-adrenal effect of adrenocorticotropic hormone.

Effects of ACTH-(1-24) on the release of noradrenaline from postganglionic sympathetic neurones were studied in rabbits. In the isolated perfused rabbit heart, ACTH-(1-24) (0.1-100 nmol/l) increased the overflow of noradrenaline elicited by sympathetic nerve stimulation at 1 Hz, an effect that persisted in the presence of propranolol and cocaine. In pithed rabbits with electrically stimulated sympathetic outflow (2 Hz), ACTH-(1-24) (0.03-1 microgram/kg per min) increased the plasma noradrenaline concentration as well as the calculated rate of entry of noradrenaline into the plasma, but decreased arterial blood pressure by a direct vasodilator effect. In anaesthetized rabbits, ACTH-(1-24) (0.1-1 microgram/kg per min) also increased the plasma noradrenaline concentration; the higher dose in addition reduced the blood pressure and increased the firing rate of renal sympathetic nerves; however, the rise in plasma noradrenaline was greater than would have been expected from the increase in sympathetic firing rate alone. It is concluded that ACTH exerts two primary effects on the cardiovascular system of the rabbit: presynaptic facilitation of the noradrenaline release and postsynaptic vasodilation. The vasodilation leads to a baroreceptor-mediated reflex increase in sympathetic tone. The low concentrations of ACTH required suggest that presynaptic facilitation may occur in vivo, at least when the secretion of ACTH is high.

Adrenergic Fibers↗
PubMed1988

ACTH increases noradrenaline release in the rabbit heart.

The effects of ACTH on the release of noradrenaline and the increase of heart rate produced by sympathetic nerve stimulation (1 Hz) were studied in isolated perfused rabbit hearts. ACTH-(1-24) 0.1-100 nmol/l increased the stimulation-evoked overflow of noradrenaline concentration-dependently, reversibly and up to two-fold. The basal outflow of noradrenaline, the basal heart rate and the stimulation-evoked increase in heart rate were not changed. Human ACTH-(1-39) also increased the evoked overflow of noradrenaline. The effect of ACTH-(1-24) 0.3 nmol/l persisted after blockade of beta-adrenoceptors with propranolol and blockade of neuronal catecholamine uptake by cocaine. ACTH-(1-24) 3 nmol/l did not change the removal of noradrenaline from the perfusion fluid, when hearts were perfused with medium containing 59 nmol/l noradrenaline. The results show that ACTH increases the action potential-evoked release of noradrenaline from cardiac postganglionic sympathetic neurones, probably by activating specific presynaptic ACTH receptors. The high potency of ACTH suggests that these presynaptic receptors may be activated in vivo by circulating ACTH under certain pathophysiological conditions.

Animals↗
PubMed1988

Peripheral sympatho-inhibitory cardiovascular effects of opioid peptides in anaesthetized rabbits.

1. Opioid agonists influence isolated cardiovascular tissues from rabbits, as well as the cardiovascular system of pithed rabbits, through presynaptic receptors on postganglionic sympathetic nerve fibres. The present experiments were carried out in order to study effects which result from activation of these receptors in anaesthetized rabbits. 2. In pithed rabbits with electrically stimulated sympathetic outflow, infusion of [D-Ala2-D-Leu5]-enkephalin (DADLE) 10 micrograms kg-1 min-1 and dynorphin-(1-13) (dynorphin) 1 microgram kg-1 min-1 decreased the plasma noradrenaline concentration, mean arterial pressure (MAP) and heart rate. The effects of dynorphin and, less completely, those of DADLE were antagonized by the peripherally selective opioid antagonists N-methyl naloxone bromide (NMN) 1.3 mg kg-1 and N-methyl levallorphan methanesulphonate (NML) 1-3 mg kg-1. 3. In pentobarbitone-anaesthetized rabbits, DADLE 3-30 micrograms kg-1 min-1 and dynorphin 0.3-3 micrograms kg-1 min-1 decreased the plasma noradrenaline concentration and MAP. The highest dose of dynorphin also decreased heart rate, whereas DADLE 10 micrograms kg-1 min-1 caused slight cardioacceleration. The effects of DADLE but not those of dynorphin decreased upon repeated administration. 4. The effects of dynorphin 10 micrograms kg-1 min-1 were abolished or greatly attenuated by NMN 1.3 mg kg-1 and NML 3 mg kg-1. In contrast, the antagonists reduced only slightly the blood pressure-lowering effect of DADLE 10 micrograms kg-1 min-1 and did not reduce significantly the effects of DADLE on the plasma noradrenaline level and heart rate. 5. It was concluded that systemically administered dynorphin produces sympatho-inhibition and an ensuing fall in blood pressure by an action at peripheral receptors, in all probability presynaptic Kappa-receptors on postganglionic sympathetic nerve fibres. The effects of DADLE are more complex and may involve both central and peripheral components.

Animals↗
PubMed1988

An in vitro model of 1-methyl-4-phenyl-pyridinium (MPP+) toxicity: incubation of rabbit caudate nucleus slices with MPP+ followed by biochemical and functional analysis.

1. Slices of rabbit caudate nucleus were preincubated for up to 24 h in vitro in the presence of the neurotoxic compound 1-methyl-4-phenyl-pyridinium (MPP+). Subsequently the levels of endogenous monoamines in the slices were determined by h.p.l.c. with electrochemical detection. MPP+, in concentrations higher than 32 nM significantly diminished the dopamine levels within the slices in a concentration- and time-dependent manner; at 32 microM the depletion was more than 95%. The concentration of the major metabolite of dopamine, dihydroxyphenyl acetic acid (DOPAC) was decreased at concentrations of MPP+ that did not alter dopamine levels. Thus, MPP+ increased the dopamine/DOPAC ratio. 2. In contrast, both 5-hydroxytryptamine (5-HT) levels and 5-HT/5-hydroxyindolacetic acid (5-HIAA) ratios were increased at nanomolar concentrations of MPP+. 5-HT was significantly reduced only at 32 microM. 3. The dopamine uptake inhibitor nomifensine reduced the depletory effect of MPP+ on dopamine and DOPAC content. 4. Following 24 h pretreatment with MPP+, the uptake of [3H]-dopamine into rabbit caudate nucleus slices was either enhanced (at 0.32 microM, 1 microM and 3.2 microM MPP+) or reduced (at 32 microM MPP+). 5. Preincubation of slices with 10 microM MPP+ for only 1 h increased their 3H-labelling (in contrast to 24 h pretreatment) whereas after 9 h no net increase was detectable. After 1 and 9 h MPP+ pretreatment, much less deaminated metabolites of [3H]-dopamine were found in the incubation medium of MPP+ treated slices than in the medium of control slices. These findings suggest that MPP+ strongly inhibits the enzyme monoamine oxidase (MAO) within dopaminergic (and 5-hydroxytryptaminergic) terminals before destroying them. 6. To validate the proposed in vitro model functionally, the electrically evoked release of [3H]-acetylcholine ([3H]-ACh) was investigated in MPP+ treated slices and controls. MPP+ reduced both the facilitatory effect of the D2-receptor antagonist domperidone and the inhibitory effect of the catecholamine uptake inhibitor nomifensine on [3H]-ACh release; effects compatible with a diminished inhibitory dopaminergic input on cholinergic neurones. 7. These findings also show that the terminal region of dopaminergic neurones, the caudate nucleus, is a site for MPP+ toxicity. The present in vitro model may be useful for investigating the effects of MPP+ and its interaction with other drugs under defined conditions.

1-Methyl-4-phenylpyridinium↗
PubMed1987

ACTH increases noradrenaline release in pithed rabbits with electrically stimulated sympathetic outflow.

ACTH 0.03-1 microgram/kg per min i.v. increased the noradrenaline spillover rate (the rate at which endogenous noradrenaline enters into plasma) and the plasma noradrenaline concentration in pithed rabbits with electrically stimulated sympathetic outflow. ACTH 0.1 and 1 microgram/kg per min decreased the mean arterial pressure (MAP). The effects of ACTH persisted in animals treated with propranolol. Corticosterone 10 micrograms/kg per min had no effect on the neurochemical and circulatory parameters. ACTH 0.03 and 1 microgram/kg per min increased plasma corticosterone and cortisol concentrations; the two doses of ACTH had approximately the same effect. The plasma corticosterone concentration reached after infusion of corticosterone 10 micrograms/kg per min was about twice that obtained after ACTH 0.03 or 1 microgram/kg per min. In a second series of experiments, a pressor dose of noradrenaline (1 or 2 micrograms/kg per min) was infused i.v. into pithed rabbits. ACTH 0.03 and 1 microgram/kg per min decreased blood pressure and increased heart rate in these animals. The results suggest that high doses of ACTH increase noradrenaline release by an action on postganglionic sympathetic neurons. The effect is probably not mediated through adrenal steroids. In addition, ACTH seems to decrease MAP and to increase heart rate through postsynaptic vascular and myocardial effects.

Adrenocorticotropic Hormone↗
PubMed1986

Opioid peptides decrease noradrenaline release and blood pressure in the rabbit at peripheral receptors.

Effects of dynorphin-(1-13), Leu5-enkephalin, D-Ala2,D-Leu5-enkephalin (DADLE), and for comparison bremazocine, on plasma noradrenaline concentration and mean arterial pressure (MAP) were studied in pithed rabbits. In the first series of experiments, the sympathetic outflow was stimulated electrically via the pithing rod at 2 Hz twice for 3 min each (S1, S2). Drugs were administered before S2. Bremazocine 10 micrograms/kg + 2 micrograms/kg/h and 100 micrograms/kg + 20 micrograms/kg/h, dynorphin 1 and 3 micrograms/kg/min, Leu5-enkephalin 100 micrograms/kg/min and DADLE 10 and 30 micrograms/kg/min all diminished the electrically-evoked increase in plasma noradrenaline and MAP. The effects were antagonized by naloxone. In the second series, an infusion of noradrenaline (2 micrograms/kg/min) was given twice for 3 min each (N1, N2). Drugs were administered before N2. Bremazocine 100 micrograms/kg + 20 micrograms/kg/h slightly enhanced the pressor effect of exogenous noradrenaline, whereas dynorphin 3 micrograms/kg/min, Leu5-enkephalin 100 micrograms/kg/min and DADLE 30 micrograms/kg/min caused no significant change. In the third series, the sympathetic outflow was stimulated continuously at 2 Hz, and the interaction of dynorphin and DADLE was studied. Dynorphin 1 microgram/kg/min and DADLE 10 micrograms/kg/min initially decreased MAP to a similar extent. The effect of DADLE faded with time. When, during continuous infusion of DADLE 10 micrograms/kg/min, and after return of MAP to the pre-DADLE level, dynorphin 1 microgram/kg/min or DADLE 10 micrograms/kg/min was infused additionally, the effect of dynorphin was unchanged, whereas that of DADLE was almost abolished. We conclude that the opioid peptides as well as bremazocine decrease action potential-evoked release of noradrenaline and, secondarily, blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Dopamine1 receptor agonist and alpha-2 adrenoceptor antagonist effects of fenoldopam in rabbits.

Neurochemical and circulatory effects of fenoldopam were studied in pithed rabbits with electrically stimulated sympathetic outflow and in strips of the rabbit pulmonary artery. In pithed rabbits, fenoldopam (1-30 micrograms/kg/min) decreased the arterial blood pressure. Fenoldopam (3-30 microgram/kg/min) also increased the norepinephrine spillover rate (the rate at which endogenous norepinephrine enters into the plasma after having been released from postganglionic sympathetic nerves) and decreased the [3H]norepinephrine plasma clearance. The selective dopamine (DA)1 antagonist SCH 23390 (bolus injection of 10 micrograms/kg followed by infusion of 2 micrograms/kg/hr) antagonized markedly and the DA2-selective antagonist domperidone (bolus injection of 200 micrograms/kg followed by infusion of 50 micrograms/kg/hr) antagonized slightly the hypotensive effect. The increase in the norepinephrine spillover rate was enhanced after treatment with desipramine. Clonidine (0.3 microgram/kg/min) reduced the spillover of norepinephrine, and this effect was abolished by fenoldopam (30 micrograms/kg/min). In pulmonary artery strips preincubated with [3H]norepinephrine, fenoldopam (10(-7) and 10(-6) M) increased the electrically evoked overflow of tritium. The effect of fenoldopam (10(-6) M) was prevented in the presence of a supramaximal concentration of clonidine (10(-5) M). The results suggest that fenoldopam lowers blood pressure mainly by activation of vascular smooth muscle DA1 receptors. In addition, however, it blocks prejunctional alpha-2 autoreceptors at postganglionic sympathetic axons.

Adrenergic alpha-Antagonists↗
PubMed1985

Neuronal and postjunctional components in the blood pressure effects of dopamine and bromocriptine in rabbits.

We have studied the contribution of neuronal and postjunctional dopamine (DA) receptors and of the DA1 and DA2 receptor subtypes to the blood pressure effects of DA and bromocriptine in the rabbit. The norepinephrine release rate, i.e., the rate of entry of endogenous norepinephrine into the plasma, was derived from the plasma level of endogenous norepinephrine and the plasma [3H]norepinephrine clearance. Bromocriptine (40 micrograms kg-1) lowered the norepinephrine release rate and the arterial blood pressure both in anesthetized rabbits and in pithed rabbits with electrically stimulated sympathetic outflow. These effects were antagonized by the selective DA2 antagonist domperidone but not by the selective DA1 antagonist SCH 23390. DA (10-160 micrograms kg-1 min-1) dose-dependently increased the norepinephrine release rate and caused only transient hypotension in anesthetized rabbits. However, after treatment with desipramine, DA did not change the norepinephrine release rate and produced a persistent fall in blood pressure. When DA and domperidone were given simultaneously to desipramine-treated rabbits, the hypotensive effect of DA was unchanged, but now DA increased the norepinephrine release rate. When DA and SCH 23390 were given simultaneously to desipramine-treated rabbits, DA failed to lower blood pressure and decreased the norepinephrine release rate. Propranolol did not change the effects of DA in desipramine-treated rabbits. These results suggest that bromocriptine decreases blood pressure by activating ganglionic and/or prejunctional, inhibitory DA2 receptors in the peripheral sympathetic nervous system. DA also activates these receptors, but in addition releases norepinephrine in the manner of an indirectly acting sympathomimetic amine and activates postjunctional vascular DA1 receptors, and the latter seems to be the main component in DA-induced hypotension.

Anesthesia↗
PubMed1984

Ethylketocyclazocine decreases noradrenaline release and blood pressure in the rabbit at a peripheral opioid receptor.

Rabbits were pithed and their sympathetic outflow was stimulated electrically via the pithing rod. Arterial blood pressure, heart rate, the endogenous plasma noradrenaline level, the plasma 3H-noradrenaline clearance and the noradrenaline release rate (the rate of entry of endogenous noradrenaline into the plasma) were determined. Ethylketocyclazocine 0.1 mg kg-1 + 0.02 mg kg-1 h-1 and 1 mg kg-1 + 0.2 mg kg-1 h-1 but not 0.01 mg kg-1 + 0.002 mg kg-1 h-1 decreased blood pressure, the endogenous plasma noradrenaline level and the noradrenaline release rate. The effects of ethylketocyclazocine 1 mg kg-1 + 0.2 mg kg-1 h-1 were antagonized by naloxone 1 mg kg-1 + 0.5 mg kg-1 h-1. Given alone, naloxone caused no change. It is concluded that ethylketocyclazocine inhibits action potential-evoked release of noradrenaline from postganglionic sympathetic neurones, and hence can lower blood pressure, by a peripheral effect, possibly mediated by opioid receptors at the terminal axons.

Animals↗
PubMed1983

Modulation of noradrenaline release in the conscious rabbit through alpha-adrenoceptors.

The effects of selective alpha 1- and alpha 2-adrenoceptor antagonists and agonists on the noradrenaline release rate and plasma catecholamine levels were studied in the conscious rabbit. The selective alpha 2-adrenoceptor blocking drugs yohimbine and rauwolscine (1 mg/kg i.v.) increased the rate of noradrenaline release into the plasma and the plasma noradrenaline and adrenaline levels. This was associated with a rise in blood pressure. The selective alpha 1-blocking drug corynanthine (1 mg/kg i.v.) had no effect. Intravenous infusions of the selective alpha 2-adrenoceptor agonist alpha-methylnoradrenaline (2 micrograms/kg per min) and the alpha 1-agonist phenylephrine (6 micrograms/kg per min) produced equipressor responses. However, only alpha-methylnoradrenaline decreased the noradrenaline release rate and the plasma noradrenaline and adrenaline levels, effects which were blocked by yohimbine. The results are compatible with, but of course do not prove the hypothesis that in the conscious rabbit, noradrenaline release from sympathetic nerves is modulated through presynaptic alpha 2-adrenoceptors. Adrenaline release from the adrenal medulla may also be subject to alpha 2-adrenergic modulation.

Adrenergic alpha-Agonists↗
PubMed1983

Evidence for a physiological role of presynaptic alpha-adrenoceptors: modulation of noradrenaline release in the pithed rabbit.

Rabbits were pithed and the preganglionic nerves at T 8 were stimulated continuously at a frequency of 3 Hz. 3H-noradrenaline was infused to reach a steady-state plasma level, from which the noradrenaline plasma clearance was calculated. The plasma level of endogenous noradrenaline was also determined and the rate of noradrenaline release into the plasma was then derived. The noradrenaline plasma clearance was decreased by guanethidine (7.5 mg/kg), desipramine (1 mg/kg), yohimbine (1 mg/kg) and rauwolscine (1 mg/kg). It was unaffected by corynanthine (1 mg/kg), prazosin (0.1 mg/kg), alpha-methylnoradrenaline (2 micrograms/kg per min) and clonidine (1 micrograms/kg per min). The electrical stimulation resulted in an increase in blood pressure without an increase in heart rate. Both adrenaline and noradrenaline were detected in the plasma. It is likely that the noradrenaline was of neuronal origin as guanethidine decreased its plasma level. The alpha 2-adrenoceptor-selective blocking drugs yohimbine and rauwolscine increased the noradrenaline release rate and only slightly decreased blood pressure. On the other hand, the alpha 1-adrenoceptor-selective blocking drugs corynanthine and prazosin had no effect on the noradrenaline release rate and decreased blood pressure more markedly. The alpha 2-adrenoceptor-selective agonists alpha-methylnoradrenaline and clonidine both decreased the noradrenaline release rate. This effect was blocked by yohimbine, and for the case of clonidine, not blocked by corynanthine. Plasma adrenaline levels were increased by yohimbine and rauwolscine, but not by corynanthine and prazosin. Clonidine reduced the plasma adrenaline level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1983

Release of [3H]-amezinium from cortical noradrenergic axons: a model for the study of the alpha-autoreceptor hypothesis.

1 [(3)H]-amezinium is taken up selectively into noradrenergic axons and their transmitter-storing vesicles and is released from these axons by action potentials. We used it as a non-alpha-adrenergic marker in order to study the alpha-adrenergic autoinhibition of noradrenaline release.2 Rat occipitocortical slices were preincubated with [(3)H]-amezinium 0.03 muM and then superfused and stimulated electrically (3 Hz for 3 min). The stimulation-evoked overflow of tritium was measured in six groups of slices: from saline-pretreated rats; from saline-pretreated rats, the slices being exposed to exogenous noradrenaline before preincubation with [(3)H]-amezinium; from saline-treated rats, slices from which were exposed simultaneously to noradrenaline and cocaine before preincubation with [(3)H]-amezinium; from rats in which noradrenaline stores had been depleted by pretreatment with alpha-methyltyrosine (alpha-MT); from alpha-MT-treated rats, the slices being exposed to noradrenaline before preincubation with [(3)H]-amezinium; and from alpha-MT-treated rats, slices from which were exposed to noradrenaline plus cocaine before preincubation with [(3)H]-amezinium.3 The stimulation-evoked overflow of tritium, expressed as a percentage of the tritium content of the tissue, was 1.15% in slices from saline-pretreated rats, and was similar in slices from saline-pretreated rats after exposure to noradrenaline or noradrenaline plus cocaine. It was 2.56% in slices from alpha-MT-treated rats, 1.20% from alpha-MT-treated rats after exposure to noradrenaline, and 2.88% from alpha-MT-treated rats after exposure to noradrenaline plus cocaine.4 Yohimbine 0.1 and 1 muM increased the stimulation-evoked overflow of tritium in slices from all groups of saline-pretreated rats and in those slices from alpha-MT rats that had been in contact with exogenous noradrenaline. Yohimbine did not change the evoked overflow in slices from alpha-MT rats that had not been exposed to noradrenaline, or had been exposed to noradrenaline plus cocaine.5 Clonidine 0.01-1 muM decreased the stimulation-evoked overflow of tritium moderately in slices from saline-pretreated rats, markedly in slices from alpha-MT-treated rats, and moderately again when the latter slices had been exposed to noradrenaline.6 It is concluded that the action potential-evoked release of [(3)H]-amezinium as well as the modulation of this release by yohimbine and clonidine depend on the presence or absence of alpha-adrenergic autoinhibition caused by the co-secretion of noradrenaline. When there is co-secretion of noradrenaline, the evoked release of [(3)H]-amezinium is relatively small, yohimbine increases the release, and clonidine can cause only moderate inhibition. When there is no or very little co-secretion of noradrenaline, the evoked release of [(3)H]-amezinium is at least doubled, yohimbine causes no further increase and clonidine produces strong inhibition.

Animals↗
PubMed1981

Functional characterization of central alpha-adrenoceptors by yohimbine diastereomers.

Rat occipital cortex slices were preincubated with [3H]noradrenaline and then superfused with medium containing 30 micrometer cocaine. They were stimulated electrically at 3 Hz. Unlabelled noradrenaline (0.1 micrometer), alpha-methyl-noradrenaline (0.01-0.1 micrometer), xylazine (0.1-10 micrometer) and guanabenz (0.01 micrometer) decreased, whereas yohimbine (0.01-1 micrometer), rauwolscine (0.01-1 micrometer), corynanthine (10 micrometers), tolazoline (0.1-10 micrometers) and azapetine (0.1-1 micrometer) increased the stimulation-evoked overflow of tritium without a change in basal outflow. Pseudoyohimbine and prazosin at up to 0.1 micrometer did not change the evoked overflow, and a higher concentrations enhanced the basal outflow of tritium. In vivo, yohimbine 10 mg/kg and rauwolscine 10 mg/kg markedly, and corynanthine 10 mg/kg slightly accelerated the alpha-methyltyrosine-induced disappearance of noradrenaline from rat whole brain. Yohimbine and rauwolscine but not corynanthine also accelerated the alpha-methyltyrosine-induced depletion of dopamine. The results add four compounds to the list of drugs with alpha-adrenoceptor affinity which inhibit (agonists) or facilitate (antagonists) action-potential-evoked release of noradrenaline in rat brain cortex. The presynaptic receptors are of the alpha 2-type. The receptors which control the activity of noradrenaline and dopamine neurons in vivo also appear to be alpha 2.

Animals↗
PubMed1976

The relation between the determinable quantities of volatile N-nitroso compounds and the peroxide number in soya bean oil.

Comparative studies of soya bean oil with and without addition of N-nitroso compounds (NDMA and NDEA) at different hydroperoxide concentrations have shown that the determinable quantities of substances having the retention time of N-nitroso compounds in soya bean oil and of nitrosoamines added to the oil are dependent upon the peroxide number. The determination was carried out by gas chromatography (nitrogen detector, nitrogen-sensitive, flame-ionization detector) prior to and following irradiation with UV light (360 nm). When the peroxide number was above 4, the determinability and the recovery were reduced by more than 60 per cent. In advanced autoxidation and after reduced recoveries, large amounts of NMDA and NDEA may be encountered for a short time. A possible linkage between N-nitroso compounds and peroxide is discussed. Comparative investigations of soya beans, crude oil, intermediates and commercially available steamed oils have revealed that the concentrations of the compounds with NDMA and NDEA properties in crude oil (peroxide number about 3) is higher than in soya beans. The recovery of these compounds is very poor in intermediate products with high peroxide numbers (about 5 to 9). However, N-nitroso compounds can be demonstrated in commercially available oils treated with steam (peroxide number about 0.7), although to a lesser extent than in crude oil.

Chemical Phenomena↗