Inheritance of low immunoreactive human plasma dopamine-beta-hydroxylase. Radioimmunoassay studies

Inheritance plays an important role in the determination of human plasma dopamine-beta-hydroxylase (DBH) enzymatic activity. It has been demonstrated that an allele (d) for very low enzymatic plasma DBH is inherited as an autosomal recessive trait. A radioimmunoassay for human DBH was developed to test the hypothesis that the presence of this allele results in a decrease in plasma DBH protein levels. The mean immunoreactive DBH (IDBH) in blood from a randomly selected population of adolescents was 824+/-38 ng/ml (mean+/-SEM, n = 134). The correlation coefficient of enzymatic DBH with IDBH for this group of 134 adolescents was 0.84 (P < 0.001). Of these subjects, 3.7% had values of < 100 ng/ml and appeared to compose a separate subgroup analogous to the 3-4% of the population that is homozygous for the allele for low enzymatic activity. There was a significant sibling-sibling correlation of IDBH values in the 14 sibling pairs included among the 134 subjects studied (r = 0.60, P < 0.025). IDBH was also measured in blood from 56 subjects homozygous (dd) for the allele for low enzymatic DBH (enzymatic activity < 50 U/ml) and in blood of 80 first-degree relatives of homozygous probands. All but two dd subjects had IDBH levels of <100 ng/ml. Results of family studies were compatible with the autosomal recessive inheritance of an allele for IDBH levels of less than 100 ng/ml which segregates with the allele for very low enzymatic activity. Average IDBH in blood of 37 obligate heterozygotes as determined by family studies (Dd) was 599+/-53 ng/ml (mean +/- SEM), significantly lower than the IDBH values found in a randomly selected population (P < 0.005). These results are compatible with the conclusion that the presence of the allele for low plasma enzymatic DBH results in a decrease in the quantity of DBH protein in human plasma.     

Analysis of mutations in the thymidine kinase gene of varicella zoster virus associated with resistance to 5-iodo-2''-deoxyuridine and 5-bromo-2''-deoxyuridine

The activity of monoamine oxidase (MAO) and dopamine-beta-hydroxylase (DBH), enzymes involved in monoamine metabolism, were studied in 29 bipolar patients (mean age = 33.12 years, SD = 7.27) who were treated with lithium carbonate and in 20 healthy volunteers (mean age = 30.05 years, SD = 6.04). Platelet MAO activity was higher after lithium withdrawal, whereas plasma DBH activity was lower in remitted euthymic bipolar patients compared with normal volunteers. During lithium treatment, platelet MAO activity decreased and plasma DBH activity increased compared with the lithium-withdrawal values. It was also observed that the activities of these enzymes in the bipolar patients during lithium treatment did not differ from those in the volunteers. Thus, platelet MAO and plasma DBH activities differed in unmedicated patients with bipolar affective disorder from those of healthy subjects. Treatment with lithium appeared to have a normalizing effect on MAO and DBH activity levels.     

The role of beta 2-adrenoceptor on the pathogenesis of insulin resistance in essential hypertension

The role of beta 2-adrenoceptor on the pathogenesis of insulin resistance in essential hypertension (EH) was explored. After the measurement of blood pressure in 15 EH patients and 8 control subjects, EH patients were divided into two groups by the elevation of plasma NE (delta NE) 5 min after standing: 7 normoadrenergic EH (delta NE < 140 pg/ml) and 8 hyperadrenergic EH (delta NE > or = 140 pg/ml). On the morning after a 12-h overnight fast, regular insulin (0.1 U/kg) was injected intravenously, and glucose disappearance rate (GDR) was measured and used as an index of insulin sensitivity. On the following day, the test was reinvestigated following the administration of mabuterol, a beta 2 agonist. Plasma growth hormone (GH), cortisol, norepinephrine (NE) and epinephrine (Epi) were measured before and after the mabuterol administration. Although there were no significant differences of basal GDR among these three groups, mabuterol induced a considerable decrease in GDR in EH patients but not in control subjects. There was no significant difference in the decrease of GDR between normo- and hyperadrenergic EH. The decrease in GDR tended to correlate with the mean blood pressure at rest in EH but not in normal subjects. Plasma glucose and serum insulin in EH patients were increased more than in normal subjects. Plasma GH, cortisol and Epi were not elevated by mabuterol, but plasma NE increased in each group, significantly in hyperadrenergic EH. There was no correlationship between the increase in plasma NE and the decrease in GDR after mabuterol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adrenal origin of the increase in plasma dopamine beta-hydroxylase and catecholamines induced by hemorrhagic hypotension in dogs

Controlled hemorrhagic hypotension in anesthetized dogs causes progressive increases in dopamine beta-hydroxylase (DBH) and catecholamine (CA) plasma levels and in heart rate. The concentration (units per milliliter) and the calculated total plasma content of DBH activity [(units circulating + reservoir + samples] increased 2.6 and 2.3 times, respectively. A significant positive correlation (P less than .001) was found between the plasma levels of DBH and CA; however, the CA plasma levels increased earlier and were of greater magnitude (10-fold) than those of DBH. These results suggest that CAs are more sensitive indicators of acute changes in adrenergic activity than DBH. Surgical bilateral adrenalectomy completely abolished the increases in circulating CA and DBH levels and in heart rate induced by the hemorrhage, independently of the percentage of blood removed. These results indicate that the adrenal glands contribute almost exclusively to the rise in plasma DBH and CA caused by the bleeding stress and that high circulating CA concentrations seem to account for the tachycardia that accompanies the hemorrhagic hypotension. The infusion of the reservoir blood with a lower DBH and CA content than that present in the animal at that time produced a rapid fall in circulating CA levels (59.2 +/- 8.9 to 10.8 +/- 3.3 ng/ml) and no change in the DBH concentration (5.43 +/- 0.42 and 5.40 +/- 0.53 U/ml). A 38% increase in the calculated total plasma content of DBH occurred with the transfusion. Due to the large size of the DBH molecules, trapping in tissues during the hemorrhagic hypotension period might have occurred. The improvement in the hemodynamic conditions caused by the transfusion would facilitate the washout of the enzyme from the tissues into the circulation.     

Laparoscopic vs conventional appendectomy--a meta-analysis of randomised controlled trials

A comparison was made of the dynamics of sympathoadrenal activity in 11 age-matched male and female rats, under basal conditions and after exposure to footshock. Rats were prepared with indwelling catheters in the tail artery 24 h before the experiment. Measurements were made of plasma corticosterone (COR), norepinephrine (NE), epinephrine (EPI), dihydroxyphenylalanine (DOPA), dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) under resting conditions, after transfer to the shock box (novelty) and at various times after footshock. Under basal conditions, males have significantly higher blood pressure and plasma DHPG/NE ratios but lower plasma levels of COR, NE and DOPAC than females. Three min after exposure to the shock chamber (novelty stress) there were significant increases in COR, EPI, NE and DHPG in both sexes, while DOPA increased only in females and DOPAC remained unchanged in both sexes. Footshock produced a further increase in EPI, NE and DOPAC within 2 min, which lasted about 15 min. There were significant sex differences in the extent and duration of the response of COR, EPI and DHPG. The data show that the female sympathoadrenal system is more reactive than that of the male to the stresses of a novel environment and footshock. The smaller DHPG/NE ratios in females at rest and after stress suggest that neuronal uptake of NE is lower in females than in males. The finding that stress produces larger increments of plasma DOPA and DOPAC in female rats indicates that tyrosine hydroxylase in the sympathetic nerve terminals and adrenal medulla may also be higher than in males.     

Selective effects on CRF neurons and catecholamine terminals in two stress-responsive regions of adult rat brain after prenatal exposure to diazepam

Earlier work demonstrated that prenatal exposure to diazepam (DZ) selectively affected the noradrenergic (NE) terminals in the hypothalamus, leading to decreased basal NE levels, turnover rate, and release in adult offspring as well as altered responses to stressors in these NE projections. The exposure also affected plasma hormonal responses to stressors. In the present work, we used immunocytochemistry to study the effects of prenatal DZ exposure on NE terminals and on corticotropin-releasing factor (CRF)-containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. DZ exposure (2.5 or 10 mg/kg over gestational days 14-20) led to a decrease in dopamine-beta-hydroxylase (DBH)-immunoreactivity (-ir) and a decrease in CRF-ir containing cells within the PVN of adult rats. The exposure also decreased DBH-ir in the ventral portion of the bed nucleus of the stria terminalis (BNST) but did not affect CRF-ir in the oval nucleus of BNST. Therefore, this study provides anatomic evidence that targeting benzodiazepine binding sites prenatally affects two neurotransmitter systems involved in responses to stressors.     

Autonomic dysfunction in patients with dementia of the Alzheimer type

Abnormalities of the noradrenergic system have been documented in the central nervous system of patients with dementia of the Alzheimer's type (DAT). To evaluate the autonomic sympathetic system in DAT, we measured lying and standing blood pressure (BP), pulse, and plasma epinephrine (E) and norepinephrine (NE) in 60 DAT patients (mean age +/- SD = 65 +/- 8 years), and 20 normal elderly controls. DAT patients had normal baseline findings (BP, pulse, NE, and E). Upon standing, plasma NE and E significantly increased in both DAT patients and controls, without group differences. However, the systolic BP response to standing was reduced in DAT patients compared with the normal controls (repeated measures ANOVA, p < 0.01). This impaired response of the systolic BP on standing was particularly evident in DAT patients with symptoms of depression. Severely impaired DAT patients did not differ in E, NE, BP, pulse, or in orthostatic changes from mild-to-moderately impaired patients. These results suggest that the sympathetic response to the stress of standing is functionally impaired in DAT. This deficit was especially evident when DAT was accompanied by depression, consistent with prior studies in non-demented depressed patients.     

Serum dopamine-beta-hydroxylase activity and blood pressure

The purpose of the studies reviewed here was to investigate the role of inheritance in the regulation of human serum dopamine-beta-hydroxylase (DBH) activity. DBH is a catecholamine biosynthetic enzyme that is localized to catecholamine-containing vesicles, is released with catecholamines from sympathetic nerves and the adrenal medulla, and is found in serum. It has been suggested that serum DBH activity might be a useful and convenient measure of sympathetic nervous system function. DBH activity was measured in blood from large, randomly selected populations of children, adolescents, and adults and in blood of relatives of children with very low serum DBH activity (less than 50 units). The results of sibship and pedigree analyses of data from families of probands with very low enzyme activity were compatible with autosomal-recessive inheritance of very low serum DBH activity. In addition, the results of studies of immunoprecipitable serum DBH were compatible with a genetically mediated decrease in the quantity of DBH protein in the blood of subjects with this allele. No significant correlation of serum DBH activity with either systolic or diastolic blood pressure was found in a large, randomly selected population of children.     

Changes in plasma dopamine-beta-hydroxylase activity during the perioperative period of cardiac surgery: an index of sympathetic nerve activity

To evaluate the usefulness of plasma dopamine-beta-hydroxylase (DBH) activity as an index of sympathetic nerve activity during cardiac operations, we examined the serial changes in plasma DBH activity, in relation to the plasma noradrenaline (NA) level and hemodynamic parameters, in patients who underwent cardiac surgery. The plasma DBH activity decreased significantly after cardiopulmonary bypass, and remained low during dopamine (DA) infusion until 72 h after the operation. However, recovery of the hemodynamic parameters, being the mean arterial pressure, heart rate and cardiac index, was seen as early as 1-3 h postoperatively. It was therefore assumed that the plasma DBH activity takes a long time to recover after an operation. The time-course changes in the plasma NA level were quite different from the changes in DBH activity, with an apparent negative correlation being observed between them. Thus, there is a possibility that exogenously administered DA, as well as increased plasma NA, might inhibit DBH activity during cardiac surgery. Moreover, since catecholamines are often administered upon completion of cardiac surgery, measurement of the plasma catecholamine level would be inappropriate for evaluating real sympathetic nerve activity. From the results of this study, it is surmised that measurement of the plasma DBH activity could be useful for estimating the intrinsic sympathetic nerve activity of patients who have undergone cardiac surgery.     

Morphine amplifies norepinephrine (NE)-induced LH release but blocks NE-stimulated increases in LHRH mRNA levels: comparison of responses obtained in ovariectomized, estrogen-treated normal and androgen-sterilized rats

In these studies we examined the temporal effects of intracerebroventricular (i.c.v.) infusions of norepinephrine (NE) on plasma LH and on LHRH mRNA levels in the organum vasculosum of the lamina terminalis (OVLT) and in neurons located in the rostral (r), middle (m) and caudal (c) preoptic areas (POA) of ovariectomized, estrogen-treated rats. Thereafter, we compared these responses to those which occur in androgen-sterilized rats (ASR). NE infusions not only increased plasma LH concentrations but within 1 h after NE, LHRH mRNA levels also were increased significantly in the OVLT and rPOA but not in the mPOA or cPOA. By 4 h, these message levels still were elevated in the OVLT and rPOA and they now also were significantly higher than control values in the mPOA and cPOA. While NE also increased LH secretion in ASR, the plasma LH concentrations obtained were markedly blunted compared to control values. Moreover, NE infusions did not alter single cell levels of LHRH mRNA in any region of the rostral hypothalamus. Previously, we have reported that morphine (s.c.) markedly amplifies NE-induced LH release and questioned whether these responses are accompanied by concomitant augmented increases in LHRH mRNA levels. Morphine alone did not affect basal LHRH mRNA or plasma LH levels. However, when rats were pretreated with morphine (-15 min) and NE was infused i.c.v. at 0 time, significant amplification of LH release occurred but, unexpectedly, morphine completely blocked NE-induced increases in LHRH mRNA levels in all of the neurons we examined. Morphine also amplified LH release in ASR but these responses were significantly less than those obtained in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma catecholamine levels in the coronary sinus, aorta and femoral vein of subjects undergoing cardiac catheterization at rest and during exercise

Plasma catecholamine (CA) levels in the coronary sinus (CS), aorta (Ao) and femoral vein (fv) were simultaneously measured in 22 patients with various heart diseases at rest and during handgrip exercise (IHG). The mean resting levels of plasma norepinephine (NE) in CS, Ao and FV were 359 +/- 49 (SEM) pg/ml, 290 +/- 27 and 234 +/- 24, respectively. The corresponding values of epinephrine (E) were 127 +/- 18 pg/ml, 186+/- 30 and 97 +/- 11, respectively. The E values in Ao were significantly greater than those in CS and in FV (p less than 0.05). IHG exercise induced an obvious elevation of plasma CA levels in every portion of the circulation studied. The mean increments of NE concentration were 81%, 54% and 67% of the resting levels at CS, Ao and FV, respectively, while IHG induced elevation of E were 70% of the resting values at each portion studied. Significant correlations were observed between individual CA concentrations in CS and in Ao, and also between those in Ao and in FV at rest. Under raised sympathoadrenal conditions, however, individual values of NE in CS failed to correlate signficantly to those in Ao and in FV, respectively. The NE output from CS was limited to only 3% and 5% of those in Ao at rest and during IHG, respectively. An actual mean increment of NE on its passing through the coronary circulation was only 2% or less of NE output in ao at both stages. It appears, thus, to be untenable that the cardiac tissue is one of the major source of circulating CA at physiological condition. From these reasons, the direct measurement of NE levels in CS may be mandatory, when plasma CA assay is designed for the purpose of studying the role of the sympathetic nerve activity in the regulation of cardiac function.     

Effect of variations in adrenocortical function on dopamine beta-hydroxylase and norepinephrine in the brain of the rat

The effect of adrenalectomy and corticosterone treatment on dopamine beta-hydroxylase (DBH) activity, catecholamine content and norepinephrine formation and metabolism were studied in the hypothalamus and other parts of the brain of male rats. Two days after adrenalectomy, there was a decrease in DBH activity in the hypothalamus and the brain stem but no change in norepinephrine or dopamine content. Conversion of intraventricularly administered tritiated dopamine to tritiated norepinephrine was slightly increased and norepinephrine was metabolized at a more rapid rate than normal. Corticosterone in a dose of 100 mg/kg increased DBH activity but decreased hypothalamic norepinephrine and copamine content. In adrenalectomized rats, smaller, more physiological doses of corticosterone did not change DBH activity or catecholamine content. The fact that norepinephrine formation and metabolism were increased at the same time that DBH activity in vitro was decreased suggests that DBH is not rate-limiting in adrenergic neurons in the hypothalamus, or that a change in the in vitro activity of the enzyme was not accompanied by a parallel change in its activity in vivo.     

Pre- and postganglionic stimulation-induced noradrenaline overflow is markedly facilitated by a prejunctional beta 2-adrenoceptor-mediated control mechanism in the pithed rat

The aim of the study was to further explore the prejunctional beta-adrenoceptor-mediated control mechanism of noradrenaline release from sympathetic nerves in response to preganglionic nerve stimulation (PNS) and local nerve stimulation of the portal vein, respectively, in the pithed rat. Baseline values as well as the increments of mean arterial blood pressure (delta-BP), heart rate (delta-HR) and plasma noradrenaline levels (delta-NA) in response to four PNS episodes (0.8 Hz, 3 ms, 75 V for 45 s at 20 min intervals), respectively, were evaluated. Fenoterol administration (0.25 mg/kg, i.v.) reduced significantly the basal blood pressure but did not alter delta-BP in response to PNS. Basal heart rate markedly increased after fenoterol without any further change in heart rate induced by PNS. The beta 1-selective antagonist CGP 20712A attenuated delta-BP in response to PNS and prevented the fenoterol-induced increase in basal heart rate. The beta 2-selective antagonist ICI 118,551 per se did not change the blood pressure and heart rate values, but antagonized the fenoterol-induced decrease in basal blood pressure. Fenoterol enhanced plasma delta-NA in response to PNS by 105% in comparison to the corresponding control value. This effect of fenoterol could be blocked by pretreatment with ICI 118,551 but not with CGP 20712A (a selective beta 1-adrenoceptor antagonist) which per se did not significantly change plasma delta-NA. Repeated local stimulation of the portal vein (S1-S3, 2 Hz, 3 ms, 10 mA, for 120 s at 30 min intervals) increased portal plasma noradrenaline without changing mean blood pressure and heart rate in pithed rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma prolactin responses to thyrotropin-releasing hormone in patients with breast cancer

Plasma human prolactin levels were measured by homologous radioimmunoassay in patients with primary breast cancer and in normal women of similar age. In normal controls mean (+/- SEM) basal plasma prolactin levels were 11.9 +/- 1.5 ng/ml and intravenous injection of synthetic thyrotropin-releasing hormone (TRH), 500 mug, caused a significant rise in plasma prolactin in all subjects examined with a maximum response of 52.6 +/- 3.3 ng/ml (mean +/- SEM). Markedly high plasma prolactin levels and exaggerated plasma prolactin responses to TRH were demonstrated in some patients with breast cancer. However, mean basal plasma prolactin levels and mean plasma prolactin increments following TRH in patients with breast cancer did not differ significantly from those in normal subjects. Plasma prolactin responses to TRH were slightly blunted during the administration of androgen in patients with breast cancer. These results suggest that some of the patients with primary breast cancer have abnormal prolactin secretion.     

The haemodynamic and antithrombotic effects of intermittent pneumatic calf compression of femoral vein blood flow. A comparison between different pump types

Postural changes in plasma renin activity were studied in three groups of age and duration-matched male diabetics (potent, impotent and with postural hypotension) and in non-diabetic control subjects. Those diabetic subjects with postural hypotension due to automatic neuropathy had no increase in plasma renin activity to the erect posture whereas both the potent and impotent groups had similar plasma renin activity responses to the control subjects. There was a significant inverse correlation between the rise in plasma renin activity on standing and the postural drop in blood pressure (r = 0.476, P less than 0.01) but no correlation with other tests of autonomic reflex function such as the Valsalva manoeuvre and blood pressure response to sustained handgrip. The results suggested that the lesion responsible for the postural hypotension is in the efferent sympathetic pathway. However, neuropathy per se did not wholly explain the decreased postural plasma renin activity response. Diabetic nephropathy, with involvement of cells of juxtaglomerular apparatus, may also be implicated.     

The fractal geometry of evolution

Many of the specific serotonin reuptake inhibitors appear to have some effect on noradrenergic function. Fluvoxamine is one of the newer agents and its specificity has not been fully assessed. Depressed patients participating in a study comparing the efficacy of fluvoxamine with imipramine and placebo collected 24 hour urine samples (N = 38) and had plasma samples drawn (N = 38) prior to and after 6 weeks of double blind treatment. Urine samples were analyzed for 24 hour output of MHPG, VMA, NMN, MN and HVA. Plasma samples were analyzed for NE levels. Imipramine treatment produced a reduction in urinary MHPG, an increase in the ratio of NMN to MHPG plus VMA, and a trend towards an increase in plasma NE which was significantly different than the effects seen in the fluvoxamine and placebo groups. There was an additional finding in the imipramine group of a significant correlation between percentage change in plasma NE and clinical improvement. Fluvoxamine treatment, on the other hand, produced no clear effect on any measure of noradrenergic function and the antidepressant efficacy of fluvoxamine was unrelated to any noradrenergic variable. These findings lend support to the hypothesis that fluvoxamine does not have significant effects on noradrenergic function.     

Geranylgeranylpyrophosphate, a metabolite of mevalonate, regulates the cell cycle progression and DNA synthesis in human lymphocytes

To determine the effect of coca chewing on heart rate (HR), mean arterial blood pressure (MAP), and plasma volume and their relationship with the hormones regulating cardiovascular and body fluid homeostasis, 16 male volunteers were examined at rest and during 1 h of cycle exercise at approximately 75% of their peak oxygen uptake in two trials separated by 1 mo. One trial was performed after the subjects chewed a sugar-free chewing gum (Coca- trial), whereas the other was done after the subjects chewed 15 g of coca leaves (Coca+), with the order of the Coca- and Coca+ trials being randomized. Blood samples were taken at rest, before (R1) and after 1-h chewing (R2), and during the 5th, 15th, 30th, and 60th min of exercise. They were analyzed for hematocrit, hemoglobin concentration, red blood cell count, plasma proteins, and for the fluid regulatory hormones, including plasma catecholamines [norepinephrine (NE) and epinephrine], renin, arginine vasopressin, and the atrial natriuretic peptide (ANP). During the control trial (Coca-), from R1 to R2, there was no significant change in hematologic, hormonal, and cardiovascular status except for a small increase in plasma NE. In contrast, it can be calculated that coca chewing at rest induced a significant hemoconcentration (-3.8 +/- 1. 3% in blood and -7.0 +/- 0.7% in plasma volume), increased NE and MAP, and reduced plasma ANP. Chewing coca before exercise reduced the body fluid shifts but enhanced HR response during exercise. These effects were not accompanied by changes in NE, epinephrine, renin, and arginine vasopressin plasma levels. In contrast, plasma ANP response to exercise was lower during the Coca+ trial, suggesting that central cardiac filling was reduced by coca use. It is likely that the reduction in body fluid volumes is a major contributing factor to the higher HR at any given time of exercise after coca chewing.     

Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetic and nondiabetic subjects

The objective of this study was to determine whether basal plasma free fatty acid (FFA) concentrations affect basal insulin secretion rates (ISRs). Effects of FFA levels on basal ISRs were evaluated by lowering basal plasma FFA levels with nicotinic acid (NA) (100-150 mg p.o., q 30 min x 4 h) in type 2 diabetic patients and in normal volunteers. Lowering of FFAs (from approximately 600 to approximately 100 micromol/l) lowered ISRs in type 2 diabetic patients during isoglycemic clamping (from 139 to 101 pmol/min; -23%; P < 0.02) and euglycemic clamping (from 99 to 63 pmol/min; -36%; P < 0.03) and in normal subjects during euglycemic clamping (from 127 to 96 pmol/min; -25%; P < 0.03). In addition, peripheral insulin concentrations decreased by approximately 30% in diabetic and nondiabetic subjects. NA had no direct effect on ISRs; that is, NA did not change ISRs when plasma FFAs were prevented from decreasing with a lipid/heparin infusion. We concluded that 1) basal plasma FFAs exerted physiologically important, long-lasting effects supporting 25-33% of basal insulin secretion in nondiabetic and diabetic subjects; 2) basal plasma FFAs were responsible for some of the hyperinsulinemia in normoglycemic obese subjects; and 3) NA had no direct effect on insulin secretion.     

Intracellular signalling by binding sites for the antipsoriatic agent monomethylfumarate on human granulocytes

Basal and stress levels of catecholamines (CA) in the adrenal glands, and circulatory levels of adrenocorticotropic hormone (ACTH) were examined in female Wistar rats aged 1, 3, 10 and 24 months. Our data showed reduction in basal dopamine (DA) concentration in adrenal glands and an increase in this catecholamine in response to stress at all ages (1, 3, 10, 24 months). The greatest levels of basal norepinephrine (NE) and epinephrine (E) concentrations in the adrenal glands were noted in intact rats at the age of 24 months. On the other hand, the stress response of NE and DA had a tendency to fall, reaching basal values at the age of 10 and 24 months of age. Basal circulatory levels of ACTH showed a reduction with age. The stress response of ACTH was reduced in animals aged 10 and 24 months. Reduced basal values of adrenal DA and increased NE and E values, suggest that there is increased adrenomedullar activity at the age of 24 months. On the other hand, the reduced or even absent stress response of NE and E observed in the adrenals, in 10 and 24 months old rats, may be of interest in considering the ability of these animals for adaptation. Basal and stress values of plasma ACTH are significantly reduced with the onset of senescence in female rats.     

Monitoring norepinephrine levels by microdialysis in the white adipose tissue of spontaneously hypertensive rats

1. To investigate whether microdialysis is suitable to monitor catecholamine in white adipose tissue of conscious rat and to assess eventual differences in norepinephrine (NE) interstitial levels, two groups of 12 male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, 14-16 weeks old, were compared. 2. A flexible microdialysis probe was implanted subcutaneously in the parascapular region, and perfused with Ringer solution (flow rate: 2.0 mu L/min). After a 20 min equilibration period, NE levels were monitored over a 120 min period; then, tyramine hydrochloride (0.1 nmol/min) was perfused for 80 min. Dialysates from each 20 min collection period were analysed by HPLC with electrochemical detection for NE. 3. Basal levels of NE (adjusted for the recovery) were higher in SHR compared to WKY (1210.0 +/- 140.5 pg/mL dialysate vs 573.3 +/- 75.8 pg/mL dialysate; P < 0.001, ANOVA). In both strains tyramine perfusion increased NE concentration in dialysates; the net (i.e. baseline subtracted) NE output was lower (76.3 pg/h, s.e.m. 22.3) in SHR compared with that shown by WKY rats (201.0 pg/h, s.e.m 18.4, P < 0.01). 4. The increased basal levels of NE observed in SHR are associated with a blunted response to tyramine challenge. Since tyramine is known to cause NE release from the cytosol but not from vesicle stores, such a blunted response is consistent with an increased turnover rate of NE or with an accelerated uptake in pre-synaptic vesicles which, together with the higher basal levels, would suggest increased noradrenergic activity.