Effect of metabolic control on urinary excretion and plasma levels of catecholamines in diabetics.

Urinary excretion and plasma levels of catecholamines were determined in 20 normal and 39 diabetic subjects to evaluate the sympathetic activity. Diabetic patients were divided into 4 groups according to the metabolic control. Sympathetic activity showed no differences between normal and subjects with chemical diabetes (group I, n = 5). In insulin-treated diabetics in good metabolic control (group II, n = 11) only urinary excretion of free norepinephrine was significantly higher than normals (p less than .05). In insulin-treated diabetics in poor metabolic control (group III, n = 16) urinary excretion and plasma levels of norepinephrine showed a marked increase over groups I and II (p less than .001). In insulin-treated diabetics with ketosis (group IV, n = 7) urinary excretion and plasma levels of both norepinephrine and epinephrine showed the highest values (p less than .001 and less than .1). Finally, in groups III and IV, after achieving improved metabolic control, a significant decrease of urinary excretion and plasma levels of catecholamines was observed. The results confirm that there is an increased rate of catecholamine release in poorly controlled diabeties and suggest a close correlation between sympathetic activity and metabolic derangement in diabetes.     

Circadian variations of catecholamines and blood pressure in patients with pseudohypoparathyroidism and hypertension

The relationship between 24-h recumbent blood pressure levels and secretory patterns of catecholamines was investigated in 4 patients with pseudohypoparathyroidism (PsHP) and hypertension and in 9 patients with essential hypertension. A clear circadian rhythm of blood pressure and catecholamines was documented in both groups with lowest levels of blood pressures and catecholamines occurring during sleep. During the 24-h period of recumbency mean arterial blood pressure (MAP) was correlated (r = 0.63, p less than or equal to 0.01) with plasma norepinephrine (N) in the patients with essential hypertension, but this correlation was weaker in patients with PsHP (r = 0.38, p less than or equal to 0.05). MAP was more closely related to plasma epinephrine (E) (r = 0.62, p less than or equal to 0.01) than to plasma NE in patients with PsHP. Plasma NE and E levels were considerably lower in patients with PsHP than in patients with essential hypertension throughout the 24-h recumbent period. The sleep-related decline in blood pressure and NE was less than in patients with essential hypertension. These results suggest that while the sympathetic nervous system may have a role in hour-to-hour maintenance of blood pressure in patients with PsHP and hypertension, it does not appear to be responsible for the elevated arterial pressure in these patients. Factors other than those investigated, such as obesity, alterations in sodium homeostasis of refractoriness of the vascular smooth muscle to the vasodilatory effect of PTH may be involved in the pathogenesis of hypertension in PsHP.     

Neuropeptide Y and natural killer cell activity: findings in depression and Alzheimer caregiver stress.

A reduction in immune function has been found in patients with a major depressive disorder and in persons undergoing severe life stress. This study investigated the association between increased sympathetic nervous system activity and reduced natural killer (NK) cytotoxicity in depression and Alzheimer caregiver stress. NK activity and plasma concentrations of epinephrine, norepinephrine, and neuropeptide Y were measured in depressed patients (n = 19) and age- and gender-matched controls (n = 19), and in Alzheimer spousal caregivers (n = 48) and matched noncaregiver controls (n = 17). Plasma levels of neuropeptide Y, but not circulating basal levels of catecholamines, were significantly (P less than 0.01) elevated in the depressed patients and in the caregivers compared with respective controls. NK activity was significantly (P less than 0.001) lower in the depressed patients than in their controls, but not different between the caregivers and the noncaregiver controls. Circulating concentrations of neuropeptide Y, but not catecholamines, were inversely correlated (r = -0.31, P less than 0.001) with NK activity. In addition, multiple regression analyses demonstrated that the significant (P less than 0.01) association between neuropeptide Y and natural cytotoxicity was independent of the relative contribution of age and basal and dynamic levels of epinephrine and norepinephrine. These findings suggest that increased sympathetic nervous system activity and the release of neuropeptide Y may be associated with the modulation of NK cytotoxicity.     

Atrial natriuretic factor and sympathetic nervous output in response to volume shifts in the immature canine circulation.

This study evaluated the immature circulation's response to acute shifts in intravascular volume with respect to atrial natriuretic factor and plasma catecholamines. Serial measurements were performed on thirteen beagle puppies during volume expansion with a saline and albumin solution followed by volume contraction with furosemide. Atrial natriuretic factor correlated with right (r = .73, p less than 0.001) and left (r = .62, p less than 0.001) atrial pressures and increased to much greater levels than previously reported for mature animals. Simultaneously, 10 puppies had a progressive decrease in plasma norepinephrine over the 60-minute infusion (p less than 0.05) while two puppies demonstrated a marked increase between the 30- and 60-minute samples. Furosemide increased urine output and reversed the hormonal changes caused by volume expansion. Thus a greatly augmented output of atrial natriuretic factor occurs in the immature canine circulation in response to increased atrial and pulmonary pressures, while sympathetic output remains unchanged or falls with increasing intravascular volume until a critical decrease in cardiac output triggers a catecholamine surge.     

QT interval variability and cardiac norepinephrine spillover in patients with depression and panic disorder

Suggestions were made that increased myocardial sympathetic activity is reflected by elevated QT variability (dynamic changes in QT interval duration). However, the relationship between QT variability and the amount of norepinephrine released from the cardiac sympathetic terminals is unknown. We thus attempted to assess this relationship. The study was performed in 17 subjects (12 with major depressive disorder and 5 with panic disorder). Cardiac norepinephrine spillover (measured by direct catheter technique coupled with norepinephrine isotope dilution methodology) was assessed before and 4 mo after treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants. The distribution of the cardiac norepinephrine spillover was bimodal, with the majority of patients having values of < or =10 ng/min. There was a positive correlation between cardiac norepinephrine spillover and corrected QT interval (r = 0.7, P = 0.03) but not with any of the QT variability measures. However, in a subgroup of five patients who had high levels of cardiac norepinephrine spillover (>20 ng/min) a tendency for a strong positive correlation with variance of QT intervals (r = 0.9, P = 0.08) was observed. There were significant correlations between the severity of depression and QT variability indexes normalized to the heart rate [QTVi and QT interval/R-R interval (QT/RR) coherence] and between the severity of anxiety and the QT/RR residual and regression coefficient, respectively. Treatment with SSRI antidepressants substantially reduced depression score but did not affect any of the QT variability indexes. We conclude that in depression/panic disorder patients with near-normal cardiac norepinephrine levels QT variability is not correlated with cardiac norepinephrine spillover and is not affected by treatment with SSRI.     

Differential plasma catecholamine and neuropeptide Y responses to acute stress in rats

Neuropeptide Y (NPY) is a vasoconstrictor present in the sympatho-adrenomedullary system and may be co-released with norepinephrine (NE) and epinephrine (EPI) during sympathetic activation. We studied plasma NPY-immunoreactivity (-ir, radioimmunoassay) and catecholamine (radioenzymatic) responses during two acute stress paradigms that differ in character, intensity, and duration. The intermittent stress of footshock (0.75 and 1.5 mA, 0.5 sec duration, at 5-sec intervals, for 5 min) evoked intensity-dependent immediate increments in plasma NE and EPI, and a delayed NPY-ir response (+0.6 +/- 0.1 pmol/ml). Prolonged (60 min) immobilization caused greater increases in plasma NE and EPI levels and no changes in plasma NPY-ir until the end of the stress session (+0.3 +/- 0.1 pmol/ml). Plasma NPY-ir responses correlated with those of NE but not with EPI suggesting a sympathetic origin for the release of the peptide. Relatively greater NPY-ir responses to footshock than to immobilization may be consistent with a preferential release of the peptide by a bursting but not continuous mode of sympathetic activation. However, it may also be due to a differential activation of the sympathetic nerves and adrenal medulla by these two stress situations.     

Vagal afferent activity and renal nerve release of dopamine

To investigate the involvement of vagal afferents in renal nerve release of catecholamines, we compared norepinephrine, dopamine, and epinephrine excretion from innervated and chronically denervated kidneys in the same rat. The difference between innervated and denervated kidney excretion rates was taken as a measure of neurotransmitter release from renal nerves. During saline expansion, norepinephrine excretion from the innervated kidney was not statistically greater than from denervated kidneys. Vagotomy increased norepinephrine release from renal nerves. Thus vagal afferents participated in the suppression of renal sympathetic nerve activity during saline expansion. No significant vagal control of dopamine release by renal nerves was detected under these conditions. Bilateral carotid ligation stimulated renal nerve release of both norepinephrine and dopamine in saline-expanded rats. The effects of carotid ligation and vagotomy were not additive with respect to norepinephrine release by renal nerves. However, the baroreflex-stimulated renal nerve release of dopamine was abolished by vagotomy. Electrical stimulation of the left cervical vagus with a square wave electrical pulse (0.5 ms duration, 10 V, 2 Hz) increased dopamine excretion exclusively from the innervated kidney of hydropenic rats. No significant change in norepinephrine excretion was observed during vagal stimulation. Increased dopamine excretion during vagal stimulation was associated with a larger natriuretic response from the innervated kidney than from its denervated mate (p less than 0.05). We conclude that under appropriate conditions vagal afferents stimulate renal release of dopamine and produce a neurogenically mediated natriuresis.     

Changes in human plasma catecholamines and dopamine-beta-hydroxylase produced by prostaglandin F2 alpha

Clinical research was conducted into the possible interrelationships between prostaglandin (PG) F2alpha and the human sympathetic nervous system. The study also permitted comparison of the relative sensitivity of 2 indicators of sympatho-adrenal activity: 1) the determination of circulating catecholamines, epinephrine and norepinephrine; and 2) analysis of plasma dopamine-8-hydroxylase activity. Intravenous PGF2alpha infusion was administered to college students 12-18 weeks pregnant to produce abortion; the results were compared to results from nonpregnant controls. Circulating norepinephrine but not plasma epinephrine or dopamine-8-hydroxylase levels were increased in response to the PG. There was no correlation between plasma epinephrine and plasma norepinephrine levels. Plasma dopamine-8-hydroxylase activity was found not to be significantly changed by pregnancy, administration of the analgesic and antiemetic, or the PG infusion. In fact, central venous dopamine-8-hydroxylase activity did not differ significantly from that of arterial blood. The PG did not affect cardiac output or maximal expiratory flow rate. It is suggested that the nausea and diarrhea accompanying PGF2alpha infusion may put stress on the sympathetic nervous activity causing the observed increase in plasma norepinephrine concentration. Since no changes in blood pressure, heart rate, central venous pressure, or cardiac output were observed, it is unlikely that PGF2alpha causes even slight impairment of sympathetic nervous system activity.     

Application of region-specific immunoassay for human chromogranin A: substantial clue for detection and measurement of chromogranin A in human plasma

Chromogranin A (CgA), a secretory protein, is co-released with catecholamines from storage vesicles. It is known to be elevated in the circulation of patients with neuroendocrine and endocrine tumors. For further investigation of the protein, especially in humans, it is essential to facilitate quantitative analysis of the protein in human biological materials. In order to introduce novel immunological methodology for this purpose, we purposely selected human CgA(344-374) for the synthetic immunogen to produce region-specific CgA antibodies. The anti-synthetic peptide antibody thus obtained made it possible to develop an immunological method for measurement and characterization of CgA in human plasma. The plasma CgA-immunoreactivity (LI) level measured by the method was 0.31+/-0.01 pmol/ml (mean+/-SEM) in normal subjects and 1.55+/-0.29 pmol/ml in pheochromocytoma. On gel chromatography and HPLC analysis of the plasma of patients with pheochromocytoma, the region-specific assay system enabled us to show the presence of N-terminal truncated CgA, besides CgA itself. By following up changes of plasma CgA-LI in a pheochromocytoma patient using samples that were collected consecutively over a two-year period, the present assay system using the region-specific antibody, anti-human CgA (344-374) serum, was confirmed to be extremely valuable for the measurement of CgA-LI in human plasma. The characteristic features and high sensitivity of the present assay system will give us a substantial clue to the detection and measurement of CgA to develop further investigation of the protein in humans.     

Influence of physical activity and dietary restraint on resting energy expenditure in young nonobese females

An understanding of the physiological and behavioral determinants of resting energy requirements is important to nutritional considerations in females. We examined the influence of endurance training and self-reported dietary restraint on resting metabolic rate and fasting plasma hormones in 44 nonobese females characterized for body composition, maximal aerobic power (VO2 max), and daily energy intake. To examine the association of metabolic rate and dietary restraint with hormonal status, fasting plasma levels of insulin, glucose, and thyroid hormones (total and free fractions of thyroxine and triiodothyronine) were determined. In univariate analysis, resting metabolic rate (kcal.min-1) was positively related to VO2 max (L.min-1) (r = 0.54; p less than 0.01). This relationship, however, was partially dependent on body size, since fat-free mass was also related to resting metabolic rate (r = 0.42; p less than 0.01) and VO2 max (L.min-1) (r = 0.75; p less than 0.01). After controlling for fat-free weight using partial correlation analysis, the relation between RMR and VO2 max was weaker but controlling for fat-free weight using partial correlation analysis, the relation between RMR and VO2 max was weaker but still significant (partial r = 0.38; p less than 0.05). On the other hand, high levels of dietary restraint were associated with higher levels of body fat (r = 0.31; p less than 0.05) and a lower resting metabolic rate (r = -0.29; p = 0.07). These associations persisted after control for differences in fat-free mass. Total energy intake as well as total and free levels of triiodothyronine were not related to resting metabolic rate or level of dietary restraint.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chromogranin A as a determinant of midgut carcinoid tumour volume

Neuroendocrine (NE) tumours are characterized by their capacity to synthesize, store and release hormonal products. These substances are stored in neurosecretory vesicles together with chromogranin A (CgA). The concentration of plasma CgA in patients with NE tumours is thought to reflect the degree of NE differentiation, total tumour burden and effect of medical treatment. The aim of this study was to analyse the correlation between tumour weight and plasma CgA levels as well as the influence of treatment with a long-acting somatostatin analogue (octreotide) using nude mice with xenografted human ileal carcinoid tumours. There was a correlation between tumour weight and plasma CgA levels in all animals (p<0.00001). In octreotide-treated mice, plasma CgA levels were significantly reduced versus untreated animals (p=0.037).

In conclusion, this study demonstrates that plasma CgA levels are closely correlated to tumour burden, and that plasma CgA is well suited for monitoring the clinical course and outcome of treatment in patients with NE tumours.     

Correlation between cardiac hypertrophy and plasma levels of atrial natriuretic factor in non-spontaneous models of hypertension in the rat

We have compared atrial and plasma concentration of atrial natriuretic factor (ANF) in 4 models of non spontaneous experimental hypertension with different pathogenic mechanisms in the rat: two-kidney, one-clip (2-K, 1-C), one-kidney, one-clip (1-K, 1-C), DOCA-NaCl and adrenal regeneration hypertension (ARH) and their respective normotensive controls. All hypertensive groups developed cardiac hypertrophy. In all hypertensive groups plasma ANF was higher than in controls. Atrial ANF concentration was lower in the right and left atrium of 1-K, 1-C rats and in the left atrium of ARH. A good correlation was found between systolic BP and plasma ANF in 2-K, 1-C (r = 0.82; p less than 0.01) and 1-K, 1-C animals (r = 0.70; p less than 0.01). This correlation was less good in DOCA-NaCl (r = 0.41; p less than 0.05) and non existent in ARH (r = 0.28; NS). A negative correlation between plasma ANF and atrial ANF concentrations was found only in the 1-K, 1-C group (r = 0.41; p less than 0.05). A good correlation between plasma ANF levels and cardiac weight was found in all groups: 2-K, 1-C (r = 0.83; p less than 0.01), 1-K, 1-C (r = 0.73; p less than 0.01), DOCA-NaCl (r = 0.69; p less than 0.01) and ARH (r = 0.71; p less than 0.01). We suggest that the release of ANF in experimental hypertension depends of the pathogenesis and could be related either to the level of BP (hence the magnitude of the left ventricular end-diastolic pressure) or to the existence of an expanded blood volume. The correlation between plasma ANF levels and cardiac hypertrophy suggests that ANF could be partially released by the ventricles.     

Differential control of adrenal and sympathetic catecholamine release by alpha 2-adrenoceptor subtypes

In the adrenergic system, release of the neurotransmitter norepinephrine from sympathetic nerves is regulated by presynaptic inhibitory alpha2-adrenoceptors, but it is unknown whether release of epinephrine from the adrenal gland is controlled by a similar short feedback loop. Using gene-targeted mice we demonstrate that two distinct subtypes of alpha2-adrenoceptors control release of catecholamines from sympathetic nerves (alpha 2A) and from the adrenal medulla (alpha 2C). In isolated mouse chromaffin cells, alpha2-receptor activation inhibited the electrically stimulated increase in cell capacitance (a correlate of exocytosis), voltage-activated Ca2+ current, as well as secretion of epinephrine and norepinephrine. The inhibitory effects of alpha2-agonists on cell capacitance, voltage-activated Ca2+ currents, and on catecholamine secretion were completely abolished in chromaffin cells isolated from alpha 2C-receptor-deficient mice. In vivo, deletion of sympathetic or adrenal feedback control led to increased plasma and urine norepinephrine (alpha 2A-knockout) and epinephrine levels (alpha 2C-knockout), respectively. Loss of feedback inhibition was compensated by increased tyrosine hydroxylase activity, as detected by elevated tissue dihydroxyphenylalanine levels. Thus, receptor subtype diversity in the adrenergic system has emerged to selectively control sympathetic and adrenal catecholamine secretion via distinct alpha2-adrenoceptor subtypes. Short-loop feedback inhibition of epinephrine release from the adrenal gland may represent a novel therapeutic target for diseases that arise from enhanced adrenergic stimulation.     

Effect of dietary proteins and carbohydrates on urinary and sympathoadrenal catecholamines

We previously observed that administration of tyrosine to rats or humans elevated urinary dopamine, norepinephrine and epinephrine levels. The present studies examine the effects on these urinary catecholamines of varying the ratio of protein to carbohydrate in the diets.Rats consumed diets containing 0, 18 or 40% protein (76, 58 and 36% carbohydrate respectively) for 8 days. The stress of consuming the protein-free food was associated with a 16% weight reduction, and with significantly lower serum, heart and brain tyrosine levels than those noted in rats eating the 18 or 40% protein diets. Absence of protein from the diet also decreased urinary levels of dopamine and DOPA but increased urinary norepinephrine and epinephrine, probably by increasing sympathoadrenal discharge; it also increased the excretion of DOPA in animals pretreated with carbidopa, a DOPA decarboxylase inhibitor. Carbidopa administration decreased urinary dopamine, norepinephrine and epinephrine as expected; however, among carbidopa-treated rats urinary norepinephrine and epinephrine concentrations were highest for animals consuming the protein-free diet, again suggesting enhanced release of stored catecholamines from sympathoadrenal cells. The changes in urinary catecholamines observed in animals eating the protein-free diet were similar to those seen in rats fasted for 5 days: dopamine levels fell sharply while norepinephrine and epinephrine increased.These data indicate that the effects of varying dietary protein and carbohydrate contents on dopamine secretion from peripheral structures differ from its effects on structures secreting the other two catecholamines. Protein consumption increases dopamine synthesis and release probably by making more of its precursor, tyrosine, available to peripheral dopamine-producing cells; it decreases urinary norepinephrine and epinephrine compared with that seen in protein-deprived animals, probably by diminishing the firing of sympathetic neurons and adrenal chromaffin cells.     

Effects of exercise on plasma catecholamine levels in the toad, Bufo paracnemis: role of the adrenals and neural control

Resting plasma epinephrine (E) and norepinephrine (N) concentrations for intact toads (Bufo paracnemis) were 5.57+/-1.0 and 0.88+/-0.38 ng/ml, respectively. Exercise induced a significant increase in heart rate, blood pressure and plasma epinephrine (about 4.3 times), whereas norepinephrine remained unchanged. The resting [E]/[N] ratio was 6.3 and increased to 32.9 during exercise. Adrenal denervation did not alter the basal plasma catecholamine or norepinephrine levels after exercise, but prevented the increase in epinephrine during exercise, suggesting that in the intact toad this increase is due to adrenal secretion whereas resting norepinephrine may be liberated by extra-adrenal chromaffin tissues. This also suggests that the adrenal glands can release selectively the two catecholamines. The increases in heart rate and blood pressure in denervated toads were not significantly different from those of intact animals, suggesting that during exercise the sympathetic nerves play the main role in inducing cardiovascular responses. Spinal transection induced a significant increase in basal norepinephrine levels, which remained elevated after exercise. Since spinal toads are unable to perform spontaneous movements it is possible that this increase may be caused by this stressful condition. The increases in heart rate and blood pressure observed in spinal toads during exercise may be due to direct mechanical effects of venous return on the heart.     

Intraovarian secretion of catecholamines, oxytocin, beta-endorphin, and gamma-amino-butyric-acid in freely moving rats: development of a push-pull tubing method

We have developed and validated a push-pull technique that allows focal perfusion of the ovary in unanesthetized freely moving rats. We have used this method to investigate the intraovarian secretion of catecholamines (dopamine, norepinephrine, epinephrine), oxytocin, beta-endorphin and gamma-amino-butyric acid (GABA) during the estrous cycle. Cycling animals were implanted with ovarian push-pull catheters and jugular vein catheters under ether anaesthesia on proestrus, estrus and diestrous Day 2. This procedure did not disrupt normal preovulatory release of prolactin and luteinizing hormone (LH). Thus, perfusion of the ovary and simultaneous monitoring of hormone levels in systemic blood in freely moving rats allow correlation of the temporal relationship of ovarian events with cyclic gonadotropin secretion. The results clearly indicate that a rise in ovarian norepinephrine occurs concomitant with the preovulatory surge in prolactin and LH. Ovarian beta-endorphin concentrations exhibit cyclic changes, whereas GABA release rates remain stable throughout the cycle. Oxytocin is secreted by ovarian tissue, and the secretion rate appears to be inversely related to prolactin. In view of the proposed involvement of ovarian nerves and particularly catecholamines in the process of follicular maturation and ovulation, our findings suggest a preovulatory activation of ovarian noradrenergic sympathetic neurons.     

Cardiovascular and adrenal medullo-sympathetic reactions to acute tobacco poisoning

We studied the effects after cigarette quicksmoking in 15 subjects on plasma catecholamines levels (epinephrine and norepinephrine), on heart rate and arterial pressure. Smoking-associated increments in mean plasma norepinephrine and epinephrine as well as in heart rate and arterial pressure were demonstrated. The lack of correlation between the increase of the adrenergic system activity and this of the hemodynamic parameters can be explained by their own different characteristics.     

Plasma catecholamine concentrations in normotensive rats of different strains and in spontaneously hypertensive rats under basal conditions and during cold exposure

Under basal conditions, the levels of circulating norepinephrine (NE) and epinephrine (E) were higher in normotensive Wistar rats of different origins than in Sprague-Dawley rats. Since the decline of ³H-NE concentration in the plasma after i.v. injection was similar in Wistar and in Sprague-Dawley rats, the higher levels of endogenous NE in the former strain probably reflect greater NE release from sympathetic nerve terminals. In normotensive Sprague-Dawley and Wistar rats, plasma NE rose to various extents during cold exposure (4°C), depending on the basal plasma NE levels. Compared with normotensive Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) had similar basal plasma E and NE concentrations, similar rates of ³H-NE disappearance, but more rapid increases to higher values of plasma NE during cold exposure. It is concluded that the basal rate of peripheral catecholamine release does not seem to be the main determining factor for arterial blood pressure in the various rat strains and that the sympathetic neuronal system of SHR is more responsive to cold exposure than that of WKY rats.     

Strain differences in rat adrenal biosynthetic enzymes and stress-induced increases in plasma catecholamines.

We have examined in two inbred rat strains basal and stress-induced increases in plasma levels of epinephrine (EPI) and norepinephrine (NE) and compared these with activities of the adrenal enzymes involved in the synthesis of catecholamines. There were no differences in basal levels of NE and EPI in plasma of adult male rats of the Wistar-Kyoto (WKY) and Brown-Norway (B-N) strains. However, following 5 min. of intermittent footshock, plasma levels of both catecholamines were twice as high in WKY rats as in B-N rats. In the adrenals of unstressed rats, activities of tyrosine hydroxylase and dopamine-beta-hydroxylase were significantly higher in B-N rats. In addition, the adrenal weights and the contents of NE but not EPI were greater in B-N rats. Thus, in these two rat strains, the capacity of the adrenal gland to synthesize and store catecholamines appeared to be inversely related to plasma levels of NE and EPI after stress. The differences between the strains appeared to be due to differences in the rates of removal of catecholamines from the peripheral circulation as well as to differences in the rate of release of catecholamines from the sympatho-adrenal medullary system. Thus biosynthetic enzyme activities need not be related directly to the capacity to release and elevate plasma levels of catecholamines following stressful stimulation.     

Influence of sodium intake on circulating levels of neuropeptide Y

Neuropeptide Y (NPY) is present in the adrenal medulla, in sympathetic neurons as well as in the circulation. This peptide not only exerts a direct vasoconstrictor effect, but also potentiates the vasoconstriction evoked by norepinephrine and sympathetic nerve stimulation. The vasconstrictor effect of norepinephrine is also enhanced by salt loading and reduced by salt depletion. The purpose of this study was therefore to assess whether there exists a relationship between dietary sodium intake and the levels of circulating NPY. Uninephrectomized normotensive rats were maintained for 3 weeks either on a low, a regular or a high sodium intake. On the day of the experiment, plasma levels of NPY and catecholamines were measured in the unanesthetized animals. There was no significant difference in plasma norepinephrine and epinephrine levels between the 3 groups of rats. Plasma NPY levels were the lowest (65.4 ± 8.8 fmol/ml, n=10, Mean ± SEM) in salt-restricted and the highest (151.2 ± 25 fmol/ml, n=14, p < 0.02) in salt-loaded animals. Intermediate values were obtained in rats kept on a regular sodium intake (117.6 ± 20.1 fmol/ml). These findings are therefore compatible with the hypothesis that sodium balance might to some extent influence blood pressure regulation via changes in circulating NPY levels which in turn modify blood pressure responsiveness.