Exercise-induced increases in atrial natriuretic factor are attenuated by endurance training.

Short-term exercise has been associated with increased plasma levels of atrial natriuretic factor, a potent dilating and natriuretic hormone. In this study, the effect of exercise training on atrial natriuretic factor release during short-term exercise was investigated in men without a history of cardiovascular or other major disease. A well trained group of 10 men who exercised an average of 6,618 kcal/week was compared with a minimally trained group of 9 men who exercised 1,479 kcal/week. Maximal oxygen uptake was 55.2 ml/kg per min in the well trained group and 42.5 ml/kg per min in the minimally trained group (p less than 0.05). Plasma for atrial natriuretic factor, norepinephrine and epinephrine was obtained at rest, at 4 min of exercise and at maximal exercise. Atrial natriuretic factor was lower at rest in the minimally trained than in the well trained men (23 vs. 35.9 pg/ml, p less than 0.05). At maximal exercise, atrial natriuretic factor increased 2.6 times the value at rest in minimally trained men (59.8 pg/ml, p less than 0.05 vs. rest), but did not change in well trained men (34 pg/ml). In minimally trained men at rest, at 4 min of exercise and at maximal exercise, plasma levels of atrial natriuretic factor correlated with heart rate, cardiac output, mean arterial pressure and plasma levels of norepinephrine and epinephrine; these correlations were not found in the well trained group. Thus, short-term exercise results in a significant increase in atrial natriuretic factor in minimally trained but not in well trained men.(ABSTRACT TRUNCATED AT 250 WORDS)

Excretion of amines and their metabolites by two patients in hepatic coma treated with L-dopa.

Two patients in hepatic coma were treated with L-dopa. The first patient showed clear clinical improvement, but the second patient did not. Analyses of urinary metabolites indicated that L-dopa was not absorbed by the second patient. There was evidence that L-dopa had the following beneficial effects in the first patient: (1) increased production of urine, which could have been accompanied by increased excretion of toxins; (2) displacement of tyramine from transmitter sites (because increased excretion of p-hydroxyphenylacetic acid, a major metabolite of tyramine, occurred during L-dopa treatment in patient 1); (3) replenishment of dopamine, and to a much lesser extent, norepinephrine, at central or peripheral neuroeffector junctions; and (4) scavenging of methyl groups by L-dopa, because ratio of methylated amines to catecholamines was higher than normal in both comatose patients before L-dopa treatment, and this ratio decreased during L-dopa treatment in patient 1.

Levodopa and deprenyl treatment effects on peripheral indices of oxidant stress in Parkinson's disease.

The oxidant stress theory of Parkinson's disease (PD) hypothesizes that levodopa treatment may be potentially harmful and this is supported by studies demonstrating levodopa toxicity to cultured dopaminergic neurons. These in vitro experiments, however, lack the physiologic protective mechanisms present in vivo. Oxyradical damage to cell membranes liberates malondialdehyde, which we measured in the serum of 27 PD patients just before and after levodopa (with carbidopa) administration. We also measured plasma products of the two routes by which levodopa potentially generated oxyradicals: (1) 5-S-cysteinyl-dopa (derived from levodopa autoxidation), and (2) 3,4-dihydroxyphenylacetic acid (DOPAC), produced by monoamine oxidase (MAO) metabolism of dopamine. Following levodopa/carbidopa administration, both of these plasma products were markedly increased; however, the mean serum malondialdehyde concentration was unchanged and remained similar to the normal control group (N=15) value. Chronic treatment with the MAO-B inhibitor, deprenyl (N=16), was not associated with any differences in serum malondialdehyde or plasma 5-S-cysteinyl-dopa concentrations compared with those not treated with deprenyl (N=11). The post-levodopa rise of plasma DOPAC was only slightly attenuated with deprenyl therapy, consistent with a predominant MAO-A effect in the circulation and peripheral organs. Thus, in contrast to in vitro studies, we did not detect evidence of oxidative damage in the circulation following levodopa administration, despite marked increase in the products of dopamine oxidative metabolism.

Intrathecal 6-hydroxydopamine or cervical spinal hemisection reduces norepinephrine content, but not the density of alpha 2-adrenoceptors, in the cat lumbar spinal enlargement.

The effect of the intrathecal administration of the catecholaminergic neurotoxin 6-hydroxydopamine, or of hemisection of the spinal cord at the Cl level, on the density of alpha 2-adrenoceptors and on the norepinephrine, dopamine, and serotonin content in the cat lumbar spinal enlargement was determined 2, 7 or 21 days after performance of each type of lesion. The intrathecal administration of 6-hydroxydopamine produced a time-dependent reduction of norepinephrine content in the cat lumbar spinal enlargement (95% reduction at 21 days) without significantly altering the serotonin content in this same tissue of the same cats. The dopamine content of the dorsal horn was not changed significantly, whereas ventral horn dopamine content was depleted after intrathecal 6-hydroxydopamine. alpha 2-Adrenoceptor binding site density was not significantly different from control either 2 or 21 days after 6-hydroxydopamine, but was increased significantly (50%) over the control density 7 days after 6-hydroxydopamine. Hemisection of the cervical spinal cord produced a bilateral 40-60% reduction of norepinephrine content in both the dorsal and ventral horns of the cat lumbar spinal enlargement 7 and 21 days later. Cervical hemisection did not significantly alter the alpha 2-adrenoceptor binding site density in these same cats either 2, 7, or 21 days after performance of the lesion. It is concluded that alpha 2-adrenoceptors located on the terminals of descending noradrenergic or other spinopetal fibers do not represent a significant fraction of the total population of alpha 2-adrenoceptors present in the dorsal or ventral cat lumbar enlargement.

The secretion of catecholamines, chromogranin A and neuropeptide Y from the adrenal medulla of the cat via the adrenolumbar vein and thoracic duct: different anatomic routes based on size.

Secretion of the adrenal medulla was stimulated in nine cats by insulin-induced hypoglycemia. Levels of catecholamines (mol. wt 153-183), neuropeptide Y (mol. wt 4254) and chromogranin A (mol. wt 48,000) were measured in concurrently collected samples of adrenolumbar venous blood and thoracic duct lymph for up to 4 h following insulin administration. Insulin-induced hypoglycemia elicited an increase in the secretion of catecholamines, which reached peak levels in the adrenolumbar venous plasma at 1.5-2 h and in the lymph at 2.5 h. Although catecholamines were the most numerous measured molecules in the lymph, levels of norepinephrine and epinephrine were 75-250-fold less than those found in the adrenolumbar venous plasma. Neuropeptide Y in the adrenolumbar venous plasma reached peak levels between 1 and 1.5 h; at this time approximately 20% of the peak venous amount was detected in the lymph. Chromogranin A was found in approximately equal amounts in both plasma and lymph; the peak level in the plasma occurred at 1.5-2 h, while that in the lymph was reached at 2-3 h. We suggest that the size of a molecule influences the route it takes following exocytosis from the chromaffin vesicle. Smaller molecules such as catecholamines may pass directly into the circulation, while larger molecules such as chromogranin A may be temporarily sequestered in the interstitial space before passing into the lymph, and hence into the circulation.

Nitric oxide modulates evoked catecholamine release from canine adrenal medulla.

Nitric oxide has various actions, acting in a neurotransmitter-like role and also as a paracrine messenger between vascular endothelial and smooth muscle cells. This study was done to determine whether endogenous nitric oxide has a role in modulating evoked catecholamine release from the canine adrenal medulla. Isolated adrenal glands were perfused with Krebs-Ringer solution as a control, or with Krebs-Ringer solution containing either N(G)-monomethyl-L-arginine (L-NMMA; 3x10(-4) M) to non-selectively inhibit nitric oxide synthase or 7-nitroindazole (10(-4) M), a relatively selective inhibitor of neuronal nitric oxide synthase. Catecholamine release was evoked using the nicotinic cholinergic agonist 1,1-dimethyl-4-phenylpiperazinium iodine. From the collected perfusate epinephrine, norepinephrine, and dopamine were measured by high performance liquid chromatography. Previous studies have shown that in the presence of L-NMMA, basal releases of epinephrine, norepinephrine and dopamine are increased. 7-Nitroindazole had no effect on basal catecholamine release, suggesting that nitric oxide from an endothelial source was responsible for the inhibition of basal catecholamine release from the adrenal medulla. Epinephrine and norepinephrine releases were augmented when either of the nitric oxide synthase inhibitors was added during submaximal nicotinic stimulation, indicating that endogenous nitric oxide inhibited release of epinephrine and norepinephrine. Both neuronal and endothelial nitric oxide synthases appeared to be responsible for this inhibition. In summary, these studies suggest that nitric oxide, from both neuronal and endothelial sources, modulates evoked catecholamine release from canine adrenal medulla, while nitric oxide from an endothelial source is most likely responsible for modulation of catecholamine release under basal conditions.

Inhibition of aromatic L-amino acid decarboxylase under physiological conditions: optimization of 3-hydroxybenzylhydrazine concentration to prevent concurrent inhibition of monoamine oxidase.

The activity of the enzyme tyrosine hydroxylase (TH; EC 1.14.16.2) is commonly studied indirectly by quantifying the formation of the product, 3,4-dihydroxyphenylalanine (DOPA), after inhibition of aromatic L-amino acid decarboxylase (AAAD; EC 4.1.1.28), the enzyme which metabolizes DOPA. This study was done to determine if the concentration of the hydrazine derivative 3-hydroxybenzylhydrazine (NSD-1015), a drug frequently used in vitro to inhibit AAAD, could be adjusted such that it would inhibit that enzyme, but would not simultaneously inhibit a second, potentially important enzyme, monoamine oxidase (MAO; EC 1.4.3.4). MAO catalyzes the formation of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylglycol (DOPEG) from dopamine (DA) and norepinephrine (NE), respectively. Five concentrations of NSD-1015 in superfusate (0.01 to 20 microM) were tested in strips of canine portal vein superfused and stimulated in vitro. DOPA, DA, NE, and DOPEG in superfusate and in the veins after superfusion were quantified by HPLC with electrochemical detection. The efficacy of NSD-1015 in inhibiting AAAD and MAO was determined by examining the levels of DOPA and DOPEG, respectively. NSD-1015, only when applied at 0.1 microM, resulted in the marked augmentation of total DOPA levels, but did not affect levels of DOPEG, which suggests that this concentration of the drug inhibits AAAD, but does not inhibit MAO. Therefore, it is concluded that, of the concentrations of NSD-1015 tested, 0.1 microM is the optimum concentration to use in this preparation for studies designed to examine TH activity by measuring DOPA after the inhibition of AAAD.

Bilateral adrenal medullary hyperplasia in multiple endocrine neoplasia, type 2: the precursor of bilateral pheochromocytoma.

An asymptomatic 12-year-old girl with multiple endocrine neoplasia, type 2, had high urinary levels of vanillylmandelic acid that suggested pheochromocytoma; she also had bilateral medullary thyroid carcinoma and hyperparathyroidism. Her mother and maternal aunt and uncle had bilateral pheochromocytoma (metastatic in the former two). Bilateral adrenalectomy was performed. Diffuse, non-nodular adrenal medullary hyperplasia was present. This hyperplasia was characterized by increased medullary mitotic activity, decreased corticomedullary ratio, increased total adrenal weight, and increased total catecholamine content (left adrenal). The results in this case suggest that diffuse hyperplasia of the adrenal medulla may be the precursor of pheochromocytoma in patients with this syndrome.

Patterns of dystonia ("I-D-I" and "D-I-D-") in response to l-dopa therapy for Parkinson's disease.

The clinical, biochemical, and pharmacologic responses to L-dopa were studied in 87 patients with Parkinson's disease. Eleven of the 87 patients had a long-duration response, 39 had a short-duration response, and 37 had a combination of both. Thirty-four of the 39 patients with short-duration response to L-dopa experienced a consistent and reproducible sequence of clinical and biochemical events after each dose, characterized by improvement of parkinsonism and a single phase of dystonia occurring during or shortly after the peak of dopa concentration in plasma and during maximal clinical improvement. We have called this the I-D-I- response, for Parkinsonism-Improvement-Dystonia-Improvement-Parkinsonism. The remaining five patients all had the onset of the disease at an unusually young age and showed a distinctly different response pattern consisting of a first phase of dystonia, before there was any improvement, followed by a phase of improvement without dystonia and then by a second phase of dystonia before the abrupt return of parkinsonism. We have called this the D-I-D response, for Parkinsonism-Dystonia-Improvement-Dystonia-Parkinsonsim. Dystonia occurs in the D-I-D- response when the concentration of dopa in plasma passes through a critical but relatively low level, whereas it remains absent as long as the concentration of dopa remains above that level. In the I-D-I- response, dystonia is avoided by keeping the plasma concentration of dopa low, in the D-I-D- response by keeping it high. It is postulated that in the D-I-D response postsynaptic depolarization blockade due to supramaximal stimulation of the neuronal system mediating dystonia occurs, whereas in the I-D-I response the postsynaptic members of the same neuronal population respond with excitation but not with depolarization blockade.

Adrenal medullary transplantation into the brain for treatment of Parkinson's disease: clinical outcome and neurochemical studies.

Transplantation of adrenal medulla into the caudate nucleus as treatment for Parkinson's disease was performed in eight patients. Although our previous 6-month follow-up revealed early modest improvement, an extension of that follow-up to 1 year disclosed no additional gains in any patient. At the end of 1 year, only one patient could be categorized as moderately improved; three patients were mildly improved, and four patients were unimproved. The rationale for transplanting adrenal medulla was to reestablish a physiologic source of dopamine to the striatum. We measured cerebrospinal fluid (CSF) and plasma catecholamines and metabolites before and after transplantation. Conjugated dopamine (the predominant form of dopamine found in the CSF) and homovanillic acid (the major dopamine metabolite) were modestly and inconsistently increased in the CSF. Conjugated and free epinephrine and norepinephrine, as well as 3-methoxy-4-hydroxyphenylglycol concentrations were not increased in CSF after graft placement, an indication that the adrenal chromaffin cells were no longer producing high levels of these nondopamine catecholamines and metabolites. CSF cortisol concentrations were not increased after transplantation, compared with values from controls, consistent with low numbers of functioning adrenal cortical cells contaminating the graft (or poor survival). Posttransplantation CSF did not induce a neurotrophic effect in cell cultures of 15-day embryonic rat dorsal root ganglion or PC12 (rat pheochromocytoma) cell lines. Survival of samples of patients' adrenal medullary tissue for 2 weeks in tissue culture attested to the viability of the graft at the time of transplantation. The relative concentrations of dopamine to epinephrine or norepinephrine increased in these cultured adrenal medullary cells, presumably because of loss of the glucocorticoid influence on catecholamine synthesis. A wide variety of factors could have contributed to our failure to replicate the earlier impressive results of adrenal-to-brain transplantation reported by others. Continued transplantation studies in animal models of parkinsonism are necessary for better elucidation of these factors.

Adrenal vein catecholamines and neuropeptides during splanchnic nerve stimulation in cats.

Splanchnic nerve stimulation in bursts at low (5 Hz) and high (50 Hz) frequency (30 V, 1 msec; train duration 1 sec; train rate 0.5/second) was employed in 10 cats under halothane anesthesia, during 10-minute periods, while blood samples were concurrently collected from the adrenal vein and femoral artery for the measurement of norepinephrine (NE), epinephrine (EPI), dopamine (DA), Met-enkephalin (ME), neuropeptide Y (NPY), peptide YY (PYY) and neurotensin (NT). In Group I (n = 5), splanchnic nerve stimulation was initially applied at 5 Hz followed after 20 min by a 50 Hz stimulus, while in Group II (n = 5) the stimulation sequence was reversed. Adrenal vein and femoral artery plasma levels of catecholamines and neuropeptides were not significantly affected by the stimulation sequence, while a significant decrease in blood pressure response was observed in Group II during the 5 Hz stimulation as compared to Group I, indicating desensitization. Splanchnic nerve stimulation at 5 Hz caused a preferential increase in adrenal vein NE (9-fold) versus EPI (7-fold) levels as compared to baseline, while 50 Hz stimulation led to further comparable increases in NE (5-fold) and EPI (6-fold) levels. Significant increases in adrenal vein DA and neuropeptide levels were only observed during 50 Hz stimulation, with DA showing a 5-fold, ME a 2.6-fold and NPY a 3-fold increase as compared to 5 Hz stimulation, and NT a 3.6-fold increase as compared to baseline. Present findings indicate different dynamics in the movement of catecholamines and neuropeptides from the adrenal.

The effects of ethanol on the efflux and release of norepinephrine and 5-hydroxytryptamine from slices of rat hypothalamus.

Studies were done to determine the effects of ethanol on release of norepinephrine, dopamine and 5-hydroxytryptamine from nerve terminals in the central nervous system. Superfused slices of rat hypothalamus were used in these studies and endogenous amines in the superfusate were quantitated using HPLC with electrochemical detection. In these experiments 'release' of transmitters was studied in the presence of amitriptyline to block neuronal uptake of amines, whereas 'efflux' was measured in its absence. A highly intoxicating concentration of ethanol (69.6 mM, 320 mg%) increased the K+-evoked release of norepinephrine, dopamine and serotonin without affecting basal release. Since this concentration of ethanol increased the basal efflux but not the basal release of 5-hydroxytryptamine, it appeared that neuronal uptake of 5-hydroxytryptamine under basal conditions may also be inhibited by intoxicating levels of ethanol.

Conjugates of biogenic amines in ventriculocisternal perfusates of conscious African green monkeys.

To determine the importance of conjugation relative to alternate metabolic pathways for the inactivation of catecholamines and serotonin, free and conjugated norepinephrine, dopamine and serotonin, together with the acid metabolites homovanillic acid and 5-hydroxyindoleacetic acid, were measured in ventriculocisternal perfusions in awake African green monkeys. Measurements were made of endogenous transmitters and their metabolites using high performance liquid chromatography with electrochemical detection. Efflux of amines and metabolites was measured both under conditions of spontaneous overflow and during release evoked by 40 mM K+ or by 5 X 10(-5) M amphetamine. Conjugated amines were of greater importance under basal conditions than during evoked release. Although more conjugated amines were produced in African green monkey than has been previously detected in other species, conjugation was still minor relative to O-methylation and oxidative deamination. When nomifensine (5 X 10(-5) M), a blocker of neuronal uptake of dopamine, was added to perfusion fluids, the efflux of free dopamine was increased. Efflux of conjugated dopamine was not decreased in the presence of nomifensine, suggesting that conjugation did not occur subsequent to reuptake of transmitter into dopaminergic neurons. Evidence is also presented that different enzymes are responsible for the conjugation of catecholamines and serotonin.

Resting and K+-evoked release of serotonin and norephinephrine in vivo from the rat and cat spinal cord.

Using a spinal superfusion system, the release of serotonin (5-HT) and norepinephrine (NE) from rat and cat spinal cord was measured using a high performance liquid chromatograph with an electrochemical detector. Resting levels of 5-HT and NE in the chloralose-urethanized rat were of the order of 0.8 and 0.4 ng/ml, respectively. Potassium (40 or 80 mM, in excess) produced a dose-dependent increase in the levels of both monoamines in the superfusate. The substitution of cobalt blocked this evoked release. Depletion of spinal 5-HT or NE by the prior intrathecal administration of 5,6-dihydroxytryptamine (5,6-DHT) or 6-hydroxydopamine (6-OHDA) reduced the resting levels of 5-HT and NE, respectively, and prevented the increase produced by excess potassium. These experiments indicate the ability to reliably collect and measure monoamines which overflow from spinal terminals and which reflect the degree of activation of the spinal monoamine system.

Release of endogenous catecholamines from slices of hypothalamus of rats.

The release of endogenous catecholamines from superfused slices of rat hypothalamus was studied under basal conditions and during release evoked by 40 mM K+. Catecholamines in superfusates, and in extracts of the tissue after stimulation, were isolated by column chromatography and quantitated by liquid chromatography with electrochemical detection. Norepinephrine (NE) was not consistently demonstrable in superfusate collected under basal conditions, but 40 mM K+ caused the release of from 2 to 4 ng/g of tissue per min. The addition of cocaine to the superfusate caused increases in basal and evoked release of NE. Epinephrine (E) could be measured in superfusates of slices from male but not female rats and then only when cocaine was added to the superfusate. Accordingly, the concentration of E in hypothalamus was greater in male rats than in female rats. Dopamine (DA) was not consistently measurable in the spontaneous overflow from slices either in the presence or absence of cocaine. K+-evoked release of DA could be demonstrated in slices from female rats. The addition of cocaine increased the evoked release of DA from slices from both sexes. Corticosterone, added to cocaine, had no effects on the efflux of any of the catecholamines. The experiments suggest that neuronal reuptake of all catecholamines is very efficient in the hypothalamus both under basal conditions and during evoked release.

Free and conjugated dopamine in human ventricular fluid.

Free dopamine and an acid hydrolyzable conjugate of dopamine were measured in human ventricular fluid specimens with a radioenzymatic assay and by high performance liquid chromatography (HPLC) with electrochemical detection. Only trace amounts of free norepinephrine and dopamine were detected in ventricular fluid from patients with movement disorders. When the ventricular fluid was hydrolyzed by heating in HClO4 by lyophilization in dilute HClO4, however, a substantial amount of free dopamine was released. Values for free plus conjugated dopamine in ventricular fluid from patients who had never taken L-DOPA ranged from 139 to 340 pg/ml when determined by HPLC and from 223 to 428 pg/ml when measured radioenzymatically. The correlation coefficient for values obtained by the two methods in the same sample of CSF was 0.94 (P less than 0.001). Patients who had been treated with L-DOPA had higher levels of conjugated dopamine in their ventricular CSF which correlated inversely with the time between the last dose of L-DOPA and withdrawal of the ventricular fluid. Additionally, one patient with acute cerebral trauma had elevated levels of free norepinephrine and both free and conjugated dopamine in his ventricular fluid. Conjugation may be an important inactivation pathway for released dopamine in man.

Neuropeptide Y release and contractile properties: differences between canine veins and arteries.

During intense sympathetic activation, as occurs during hemorrhage, veins constrict to a greater degree than do arteries. This study determined if differences in the amounts or actions of the sympathetic cotransmitter neuropeptide Y released from perivascular nerves could contribute to these differences. Strips of canine mesenteric and popliteal arteries and of saphenous and portal veins were superfused, and the releases of noradrenaline and neuropeptide Y evoked by transmural stimulation were assessed. Both compounds were released in greater amounts in the veins than in the arteries. In other experiments rings of each vessel were mounted in organ chambers for isometric-tension recording. Neuropeptide Y (up to 10(-4) M) did not contract any vessel; however, at 3 x 10(-7) M it shifted the frequency-response and concentration-response curves to noradrenaline in the arteries only. In the veins neuropeptide Y had no postsynaptic effect on strong contractions. These results suggest that neuropeptide Y functions locally to affect vasoconstriction of the arteries studied, and may have a different role in the veins. Further, processes involving neuropeptide Y do not appear to account for the differences in responsiveness of these arteries as compared to the veins during intense sympathetic stimulation.

Drug-induced alterations in the efflux of 5-hydroxytryptamine and of 5-hydroxyindoleacetic acid into superfusates of the rat spinal cord.

The effect of dl-p-chloroamphetamine, fluoxetine and probenecid on the efflux of endogenous 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid (5HIAA) into superfusates of the spinal cord of anesthetized rats was examined. Mean basal efflux of 5HT and 5HIAA was 0.27 and 15.56 ng/ml superfusate, respectively. The addition of dl-p-chloroamphetamine to the superfusate produced a dose-dependent increase in the efflux of 5HT into the superfusate, but did not increase the efflux of 5HIAA. Probenecid (200 mg/kg i.p.) increased the basal efflux of both 5HT and 5HIAA as compared to control values. When administered systemically, fluoxetine (10 mg/kg i.p. or s.c.) decreased the basal efflux of 5HIAA, but did not alter the basal efflux of 5HT as compared to control values. In contrast, when administered in the superfusate, fluoxetine produced a dose-dependent increase in the basal efflux of 5HT, but did not alter the basal efflux of 5HIAA. The release of 5HT produced by the addition of 2.5 X 10(-4) M dl-p-chloroamphetamine to the superfusate was not prevented in rats pretreated systemically with fluoxetine, although when administered in the superfusate fluoxetine inhibited the dl-p-chloroamphetamine-induced release of 5HT.

Sympathetic stimulating effects of sufentanil in the cat are mediated centrally.

The hemodynamic and adrenal secretory response to sufentanil (25 micrograms/kg i.v.) was evaluated during halothane anesthesia in 3 groups of cats: group I, n = 5, control; group II, n = 4, naloxone pretreatment (3 mg/kg i.v.); and group III, n = 5, acute spinal transection at T3-4. Administration of sufentanil in intact cats (group I), caused a significant increase in mean arterial blood pressure and adrenal vein plasma levels of norepinephrine, epinephrine, dopamine, and Met-enkephalin. These effects were abolished in naloxone-pretreated cats (group II). Following spinal transection (group III), sufentanil evoked a significant increase in blood pressure and heart rate, but no change in adrenal hormone levels. Intraventricular injections of sufentanil suggest that these sympathetic stimulating effects are mediated at central sites in proximity to the lateral and third ventricle.

Plasma catechols and monoamine oxidase metabolites in untreated Parkinson's and Alzheimer's diseases.

Prior studies have documented functional and pathological compromise of the peripheral sympathetic nervous system in patients with Parkinson's disease, suggesting the possibility of reduced catecholamine release into the circulation. We measured free plasma catechols in early and untreated patients with Parkinson's disease, but found no evidence of reduced concentrations, compared to control subjects or a group of patients with probable Alzheimer's disease. Rather, there was a significant elevation of plasma norepinephrine within the Parkinson's disease group. Furthermore, 6 of 15 untreated Parkinson's disease patients (40%) displayed markedly elevated plasma concentrations of the catecholamine MAO metabolites, DOPAC or DOPEG. Despite this finding, platelet MAO-B activity measured in these and all other Parkinson's disease patients fell well within the range of the control subjects, and was also statistically similar to the group with Alzheimer's type dementia. Plasma dopa levels were similar in all groups, whereas the majority of patients in the three groups had plasma free dopamine and epinephrine concentrations below the limits of detection. These trends toward increased, rather than decreased, circulating catechol concentrations suggest that peripheral sympathetic nervous system catecholamine production and release is not severely compromised in patients with early Parkinson's disease. In addition, we were unable to confirm certain previous reports of elevated MAO-B activity in patients with Parkinson's or Alzheimer's diseases.