Differential effects of experimentally induced blood pressure changes on the release of catecholamines in hypothalamic and limbic areas of rats

The effects of longer lasting blood pressure changes on the release of endogenous catecholamines (CA) in limbic and hypothalamic areas were studied in anaesthetized rats. For this purpose the central nucleus of the amygdala (AC), ventral hippocampus (VH) and medial hypothalamus (MH) were simultaneously superfused through push-pull cannulae with artificial cerebrospinal fluid and the release of the endogenous catecholamines dopamine (DA), noradrenaline (NA) and adrenaline (A) was determined before and after blood pressure manipulations. A fall in blood pressure elicited by the ganglionic blocking agent chlorisondamine resulted in different changes of the various CA release patterns in AC. Short lasting increased CA release rates as compared to prehypotension levels could be observed in the hippocampus. The activity of catecholaminergic neurons in MH remained unchanged. A rise in arterial blood pressure induced by intravenous injection of tramazoline did not change the release rates of DA in all 3 brain areas studied. In hippocampus, NA levels in the superfusates decreased initially during hypertension but returned to normal values 40 min after drug injection. In the late phase of hypertension increased rates of release of NA in the amygdala and of A in the hypothalamus could be observed. The different patterns in the release of CA suggest that DA, NA and A are differentially implicated in the regulation of experimentally induced blood pressure changes.     

Capillary-venous differences of free plasma catecholamines at rest and during graded exercise

Levels of free plasma catecholamines were simultaneously determined in 10 cyclists using capillary blood from one ear lobe and venous blood from one cubital vein. Catecholamine concentrations were higher in the ear lobe blood than in the venous blood at rest and during graded exercise. Average differences amounted to 1.7 nmol X 1(-1) (dopamine), 2.1 nmol X 1(-1) (noradrenaline) and 1.9 nmol X 1(-1) (adrenaline) at rest and increased only to 8.8 nmol X 1(-1) for noradrenaline during exercise. We assume that higher concentrations of dopamine and adrenaline in the capillary blood point to a significant neuronal release of these catecholamines, similar to noradrenaline. Catecholamine concentrations in capillary blood may better reflect sympathetic drive and delivery of catecholamines to the circulation than the concentrations in venous blood.     

Endogenous Noradrenaline and Dopamine in Nerve Terminals of the Hippocampus: Differences in Levels and Release Kinetics

The presence and release of endogenous catecholamines in rat and guinea pig hippocampal nerve terminals was studied by fluorimetric HPLC analysis. In isolated nerve terminals (synaptosomes) the levels and breakdown of endogenous catecholamines were determined and the release process was characterized with respect to its kinetics and Ca2+ and ATP dependence. Endogenous noradrenaline and dopamine, but not adrenaline, were detected in isolated hippocampal nerve terminals. For dopamine both the levels and the amounts released were more than 100-fold lower than those for noradrenaline. In suspension, released endogenous catecholamines were rapidly broken down. This could effectively be blocked by monoamine oxidase inhibitors, Ca(2+)-free conditions, and glutathione. The release of both noradrenaline and dopamine was highly Ca2+ and ATP dependent. Marked differences were observed in the kinetics of release between the two catecholamines. Noradrenaline showed an initial burst of release within 10 s after K+ depolarization. The release of noradrenaline was terminated after approximately 3 min of K+ depolarization. In contrast, dopamine release was more gradual, without an initial burst and without clear termination of release within 5 min. It is concluded that both catecholamines are present in nerve terminals in the rat hippocampus and that their release from (isolated) nerve terminals is exocytotic. The characteristics of noradrenaline release show several similarities with those of other classical transmitters, whereas dopamine release characteristics resemble those of neuropeptide release in the hippocampus but not those of dopamine release in other brain areas. It is hypothesized that in the hippocampus dopamine is released from large, dense-cored vesicles, probably colocalized with neuropeptides.     

Changes in plasma free and sulfoconjugated catecholamines before and after acute physical exercise: experimental and clinical studies.

To elucidate whether sulfoconjugated catecholamines in plasma, especially dopamine, serve as a source of free catecholamines, we examined the change in afterload on the deconjugating activity of catecholamines in isolated Langendorff perfused rat hearts. Dopamine-sulfate was administered under ordinary or high-work-load conditions. Free dopamine in the effluent was increased by the high-work-load of the hearts, whereas conjugated dopamine showed an apparent decrease. These results indicate the possibility that deconjugation of sulfoconjugated catecholamines is accelerated by a high-work-load. To obtain further evidence in humans, we also examined the changes in the plasma levels of free and sulfoconjugated catecholamines in healthy volunteers before and after marathon running. Free dopamine increased 1.99-fold from the baseline value after exercise, whereas conjugated dopamine decreased by 12%. Similarly, the plasma levels of free noradrenaline and adrenaline increased after exercise to 2.45- and 1.51-fold their respective baseline values, while conjugated noradrenaline and adrenaline both decreased. These clinical results, as well as those of the experimental studies, suggest that the increase in plasma free catecholamines after exercise is due not only to increased release from the sympathoadrenal system but also to accelerated conversion from sulfoconjugated catecholamines in the plasma.     

In vivo release patterns and cardiovascular properties of inhibitory and excitatory amino acids in the hypothalamus

Summary The posterior hypothalamus of conscious, freely moving rats was superfused with artificial cerebrospinal fluid through a push-pull cannula and the release of amino acids was determined in the superfusate. Under basal conditions, the release rates of taurine, GABA and glutamate fluctuated according to ultradian rhythms with different frequencies. Hypothalamic superfusion with veratridine or high concentrations of potassium choride enhanced the release rates of taurine, GABA and glutamate in a concentration-dependent way. Tetrodotoxin decreased the basal release rates of the three amino acids. The release of arginine was not influenced significantly by these compounds. A fall of blood pressure elicited by intravenous infusion of nitroprusside decreased the release rates of GABA and taurine and enhanced the release of glutamate. Infusion of noradrenaline increased blood pressure and release rates of GABA and taurine, while the release of glutamate was not influenced. Neither the pressor, nor the depressor responses to drugs influenced the release of arginine in the hypothalamus. It is concluded that the inhibitory amino acids taurine and GABA released from hypothalamic neurons possess a tonic hypotensive function. The excitatory amino acid glutamate, released from glutamatergic neurons of the hypothalamus, seems to possess a hypertensive function in counteracting a fall of blood pressure.This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung. These results were presented at the Third International Congress on Amino Acids, Vienna, August 1993     

Adrenomedullary origin of the hindquarter vasodilation during the transposition response of the rat

Transposing a rat from the home cage to a new cage produces a cardiovascular response (transposition response) characterized by an increase in hindquarter blood flow with unchanged systemic arterial pressure. Arterial blood samples were collected from rats before and during this response for radioenzymatic assay of catecholamines. During the transposition response, the concentration of adrenaline and noradrenaline in plasma increased about six- and two-fold, respectively. Ablation of the adrenal medulla prevented these changes in plasma catecholamine concentration. Constant i.v. infusion of adrenaline, at rates producing a hindquarter flow approximately matching that observed during the transposition response, evoked an increase in plasma adrenaline concentration also approximately matching the increase observed during the transposition response. It is concluded that the increase in plasma adrenaline secreted from the adrenal medulla is the main cause of the increase in hindquarter blood flow in the transposition response.     

Effect of thyroidectomy on cardiovascular responses to hypoxia and tyramine infusion in fetal sheep

Fetal sheep were thyroidectomized at 80 days' gestation and reoperated at 118-122 days for insertion of vascular catheters. The effects of hypoxaemia and intravenous tyramine infusion on plasma catecholamine concentrations, blood pressure and heart rate were then determined in experiments at 125-135 days' gestation. Age matched intact fetuses were also studied. Thyroidectomy was associated with increased concentrations of noradrenaline, adrenaline and dopamine in some thoracic and abdominal organs, increased noradrenaline concentrations in the cerebellum, and decreased adrenaline concentrations in the hypothalamus, cervical spinal cord, and superior cervical and inferior mesenteric ganglia. Arterial pressure was significantly lower in the thyroidectomized fetuses (34.0 +/- 0.15 mmHg) than in intact fetuses (44.7 +/- 0.2 mmHg; p less than 0.001). In contrast, plasma noradrenaline concentrations were significantly higher in the thyroidectomized fetuses (2.04 +/- 0.25 ng/ml) compared to the intact fetuses (0.99 +/- 0.08 ng/ml; P less than 0.001). In the intact fetuses there was a significant increase in plasma noradrenaline concentration and blood pressure during hypoxaemia, and bradycardia at the onset of hypoxaemia. In contrast, in the thyroidectomized fetuses hypoxaemia did not cause significant change in plasma catecholamine concentrations, blood pressure or heart rate. Infusion of tyramine produced a 1.9-fold increase of plasma noradrenaline in thyroidectomized fetuses compared to a 9.2-fold increase in the intact fetuses (P less than 0.05). Tyramine infusion caused a similar proportional increase of blood pressure in both thyroidectomized and intact fetuses. Heart rate decreased during the tyramine-induced hypertension in the intact fetus, but increased in the thyroidectomized fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Unstimulated and Amphetamine-Stimulated Release of Endogenous Noradrenaline and Dopamine from Rat Brain In Vivo

Abstract: The in vivo release rates of endogenous noradrenaline from the hypothalamus and dopamine from the caudate nucleus of the rat have been determined. Artificial CSF perfusates collected from a push-pull cannula inserted into specific areas of the brain were assayed for the amines by a sensitive radioenzymatic procedure. The release rates of noradrenaline and dopamine into artificial CSF perfusates were 38 ± 6 and 46 ± 6 pg/h (225 ± 36 and 301 ± 39 fmol/h), respectively; when 0.5 mM amphetamine was added to the CSF, the release rates of noradrenaline and dopamine increased to 176 ± 50 and 1183 ± 453 pg/h (1041 ± 296 and 7732 ± 2961 fmol/h), respectively.     

Action of dopamine on the human iris

Dopamine eye drops produce marked dilatation of the pupil in man. This mydriatic effect is inhibited by pretreatment with guanethidine. It is therefore concluded that dopamine acts indirectly via adrenergic nerve endings, rather than exerting a direct effect on adrenergic receptors in the dilator pupillae muscle. In this respect dopamine resembles the phenyl-alkylamines, such as tyramine, rather than the catecholamines, adrenaline and noradrenaline.If dopamine acts by releasing noradrenaline from adrenergic nerve endings, high concentrations of dopamine could lead to depletion of noradrenaline stores, since synthesis might be unable to keep pace with release. This could be the explantion for the orthostatic hypotension found in patients taking L-dopa for Parkinsonism.     

Effects of lead exposure on rat brain catecholaminergic neurochemistry

1. The effects of lead on catecholaminergic neurotransmission have been investigated. 2. Using the rat as a model, animals were exposed both acutely and chronically to lead. The levels of catecholamines, noradrenaline, adrenaline, and dopamine along with the activities of tyrosine hydroxylase and phenylethanolamine-N-methyl transferase were measured in 5 brain regions--cerebral cortex, brainstem, hippocampus, anterior and posterior hypothalamus. 3. A lead related reduction in the activity of tyrosine hydroxylase was observed in association with alterations in steady-state levels of the catecholamines in the posterior and anterior hypothalamus. 4. Thus, lead exposure, known to result in behavioural changes, is associated with localised neurochemical effects on the hypothalamus.     

Effects ofp-chlorophenylalanine on cortical monoamines and on the activity of noradrenergic neurons

The catecholamines noradrenaline, dopamine, adrenaline, the indoleamine 5-hydroxy-tryptamine (5-HT; serotonin), and some of their major metabolites were assayed, using high performance liquid chromatography (HPLC), in the neocortex of normal rats as well as in animals in which 5-HT synthesis had been inhibited withp-chlorophenylalanine. Besides important depletions in serotonin and in 5-hydroxyindole-3-acetic acid, noradrenaline levels were significantly reduced, but the content in 3-methoxy-4-hydroxyphenylglycol was increased, indicating an augmented utilization of this amine. The levels of dopamine and 3-methoxytyramine were also reduced, although homovanillic acid and 3,4-dihydroxyphenylacetic acid levels remained constant. The spontaneous unitary activity of identified noradrenergic neurons in the Locus coeruleus was increased, indicating an hyperactivity of this system. These results can be interpreted in relation to functional interactions between the catecholamines and serotonin; i.e.: a decrease in endogenous serotonin results in the loss of a negative feedback control of noradrenaline release.Special Issue dedicated to Prof. Eduardo De Robertis.     

Neurochemical Mechanisms Underlying Alcohol Addiction: Model Experiments on Rats

We measured the activities of the main alcohol-metabolizing enzymes (alcohol dehydrogenase, AlDH, and aldehyde dehydrogenase, AdhDH) in the blood serum, comparing these indices with the contents of ethanol and its main metabolite, acetaldehyde (AcAdh), in the blood, and also measured the contents of catecholamines (adrenaline, noradrenaline, and dopamine) in the blood and in different brain structures (hypothalamus, midbrain, and neocortex) of rats in the states of acute alcohol intoxication and chronic alcohol addiction. It was shown that, because of dissimilar changes in the activities of AlDH and AdhDH under conditions of alcohol intoxication, the dynamic balance between endogenous ethanol and AcAdh existing in the norm is disturbed, which results in an increase in the level of AcAdh. Such a phenomenon probably is one of the crucial factors underlying the development of alcohol addiction.     

A sensitive method for the determination of plasma catecholamines using liquid chromatography with electrochemical detection

Simple and sensitive methods for the determination of plasma catecholamines are of great interest since the level of catecholamines in plasma reflects the activity of the sympatho-adrenal system. In the present work a previously described procedure based on high pressure liquid chromatography with electrochemical detection has been adapted for assay of plasma catecholamines. This method permits simultaneous detection of noradrenaline, adrenaline and dopamine in concentrations down to 0.1 nmol/1 in less than one ml plasma.     

Cardiovascular, metabolic and endocrine effects of chemical sympathectomy and of adrenal demedullation in fetal sheep

A procedure in fetal sheep for causing peripheral sympathectomy by regular intravascular guanethidine sulphate administration and for causing adrenal demedullation by intragland injection of acid formalin is reported. Demedullation substantially removed adrenaline from the fetal circulation, but has a small effect only on noradrenaline. Plasma noradrenaline levels were depressed by 50% when demedullated fetuses were also subject to peripheral sympathectomy by guanethidine sulphate treatment. This provides some evidence that the paraganglia in the sheep fetus contributes to resting plasma catecholamines. Furthermore the ability of adrenal demedullation to increase markedly this pool of extra-adrenal chromaffin tissue indicates that in the fetus adrenal activity regulates the growth of these para-aortic bodies. In response to sympathectomy plasma vasopressin concentrations rose substantially, whilst adrenal demedullation caused a small rise. Demedullation and sympathectomy depressed fetal plasma glucose and elevated plasma cortisol. In both sympathectomised and adrenal demedullated fetuses resting heart rate and blood pressure was not depressed. However in those with a depleted peripheral nervous system periods of cardiovascular instability were apparent after 2-3 days of treatment with guanethidine sulphate. Hence there were regular episodes where fetal blood pressure and heart rate fell sharply followed 60-90s later by very large increases in blood pressure sustained for up to 10 min and associated with substantial production of plasma vasopressin and catecholamines. These results show that fine cardiovascular control in the fetus requires an intact sympathetic system as the endocrine system is too slow responding to effectively maintain reflex vascular control.     

Catecholamines increase urine formation in isolated toad (Bufo marinus) kidneys perfused at constant rate

Infusion of catecholamines into isolated kidneys of the toad (Bufo marinus) perfused at constant rate, produced increased arterial pressure accompanied by increased glomerular filtration rate, urine formation rate and sodium excretion. These parameters were all increased by arterial infusion of adrenaline or noradrenaline, or by infusion of adrenaline via the renal portal veins. Portal venous pressure increased slightly after arterial or portal infusion of adrenaline, but decreased after arterial infusion of noradrenaline. Estimation of segmental pressure gradients indicated that the efferent glomerular arterioles were selectively constricted by low concentrations of adrenaline or noradrenaline (3 X 10(-9), 3 X 10(-8) mol l(-1)). Higher concentrations of these amines constricted the preglomerular, as well as the postglomerular vasculature. These results demonstrate that the pericytes and/or endothelial cells which form the walls of the efferent arterioles in B. marinus are capable of active contraction.     

Blood flow and catecholamine concentration in bovine and caprine skin during thermal sweating

1. Blood flow and the concentrations of noradrenaline, adrenaline and dopamine were determined in the skins of cattle and goats, before, at the onset of and 3 hr after commencement of sweating induced by heat exposure (40 degrees C). 2. The onset of sweating in both cattle and goats was associated with a rise in cutaneous blood flow, which was thus independent of sweat pattern. Cutaneous blood flow was also higher at 40 degrees C than at 15 degrees C. 3. The predominant catecholamine in the skin of both species was dopamine, which in the goat increased in concentration in the warm environment. 4. There was no clear evidence of a change in the amount of any of the cutaneous catecholamines during exposure to 40 degrees C, although there was a consistent tendency for the concentrations of adrenaline in the calf and noradrenaline in the goat, to fall during the onset of sweating.     

Neuropeptide tyrosine (NPY)-induced potentiation of the pressor activity of catecholamines in conscious rats

IV bolus administration of 2.5-50 micrograms NPY (0.6-12.5 nmol) to conscious rats produced a dose- and time-dependent increase in systolic and diastolic blood pressure. Following priming with 2.5 micrograms NPY, or larger doses, the subsequent administrations of noradrenaline produced pressor responses that were potentiated both in magnitude and duration. The NPY-induced potentiation of the pressor response to noradrenaline was dose-dependent and extended to the pressor action of adrenaline and angiotensin II but not to the hypotensions produced by bradykinin or isoproterenol. The potentiation was not related to the fact that multiple doses of catecholamines were repeated. Reserpine did not substantially modify the NPY-induced potentiation of the pressor activity of the catecholamines. Chemical sympathectomy following 6-hydroxydopamine caused a marked supersensitivity to the catecholamines and NPY but obliterated the NPY-induced potentiation of the pressor effect of adrenaline. Nifedipine reduced the pressor action of the catecholamines and NPY but did not attenuate the NPY-induced potentiation of the pressor action of catecholamines. It is concluded that the acute pressor effect of NPY and of the potentiation of the catecholamine pressor effects involve different mechanisms.     

Olfactory sensitivity to catecholamines and their metabolites in the goldfish

The current study assessed the olfactory sensitivity of the goldfish (Carassius auratus L.) to the catecholamines, their immediate precursors and metabolites by use of the electro-olfactogram (EOG). The olfactory system of the goldfish was found to be sensitive to both adrenaline and dopamine with thresholds of detection of 10(-7.8) and 10(-7.9) M respectively, but less so to noradrenaline (threshold of detection 10(-6.3) M). The 3-O-methoxy metabolites (metadrenaline, normetadrenaline and 3-O-methoxytyramine) evoked larger amplitude EOGs than the non-metabolized form with lower thresholds of detection. However, the olfactory system was less sensitive to the amino acid precursors L-tyrosine and L-DOPA, and markedly less so to the alpha-deaminated metabolites (3,4-dihydroxyphenyl glycol, 3,4-dihydroxy mandelic acid and dihydroxyphenyacetic acid). Sensitivity to metabolites, both alpha-deaminated and 3-O-methoxylated, was similar to the alpha-deaminated forms. Cross-adaptation studies suggested that, while there is some degree of commonality of the receptor mechanisms with L-tyrosine and L-serine, a proportion of the response to the catecholamines is due to distinct receptor subtypes. Similarly, the 3-O-methoxy metabolites also had (a) separate receptor mechanism(s), although, again, there was overlap with the adrenaline/dopamine receptor site(s). Presence of the alpha-adrenoreceptor antagonist prazosin or the peripheral DA(2) dopamine receptor antagonist domperidone caused partial attenuation of the EOG responses to adrenaline and dopamine, but had much less effect on the responses to their 3-O-methoxy metabolites. The beta-adrenoreceptor antagonist sotalol had no such effect. This suggests that the olfactory catecholamine receptors are structurally and functionally distinct from systemic adreno- and dopamine receptors. The current study raises the possibility that release of catecholamines or their 3-O-methoxy metabolites to the water may play a role in chemical communication.     

Caffeine Ingestion by Rats Increases Noradrenaline Turnover and Results in Self-Biting

The effects of caffeine on the activity of central and peripheral catecholaminergic structures have been studied in rats ingesting high doses of caffeine. The activities of the enzymes tyrosine hydroxylase and dopamine-beta-hydroxylase were measured as well as 3,4-dihydroxyphenylethylamine (dopamine), adrenaline, and noradrenaline concentrations, in brain (striatum and hypothalamus), heart, and adrenal gland. At the peripheral level, we observed a significant increase in the dopamine and adrenaline plus noradrenaline content in the heart, but an increase in dopamine content only was found in the adrenal gland. Dopamine-beta-hydroxylase activity in serum was increased, but the only significant enzymic change in brain was an increase in the dopamine-beta-hydroxylase activity of the hypothalamus. However, an increase in catecholamine content was observed in both structures of the brain. These data suggest that the mechanisms involved in caffeine-induced self-biting in rats are not limited to the dopaminergic system, because we have also observed an increase in noradrenaline turnover.     

Catecholamines in sow graafian follicles at proestrus and at diestrus

Endogenous dopamine, noradrenaline, and adrenaline were detected in the sow graafian follicular wall and in the follicular fluid. Noradrenaline represented the highest level and adrenaline the lowest. Dopamine and noradrenaline concentrations found in the follicular fluid were lower at early proestrus than at mid-diestrus, whereas adrenaline levels in the fluid did not differ at either stage of the estrous cycle. The sow follicular wall contained less dopamine, noradrenaline and adrenaline at early proestrus than at mid-diestrus. Concomitantly, a decrement of [3H]-dopamine and [3H]-noradrenaline uptake, and of dopamine-beta-hydroxylase activity was detected at early proestrus compared to levels detected at mid-diestrus. The findings in sow graafian follicles show the existence of relationships between hormonal status, dopamine, noradrenaline and adrenaline endogenous levels and uptake, and dopamine-beta-hydroxylase activity. Possible links between estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels during the pig estrous cycle and ovarian catecholamines are discussed, as is a plausible involvement of these neurotransmitters in the contractile activity of the theca layer and the processes of follicular rupture and ovulation.