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At least 19 recordsLinked to original sources
PubMed1979

Vascular compartmentalization of plasma norepinephrine in normal man: the relationships between venous and arterial norepinephrine concentration and the urinary excretion of norepinephrine.

To examine whether the concentration of NE in human plasma is dependent on the vascular source of the sample and to examine the contribution of the kidney to urinary NE, 14 normal men were studied. Plasma samples were obtained from a superficial forearm vein, and radial artery and urine samples were obtained during 1 hr of recumbency and 1 hr of upright posture. The Vne was greater than Ane during both recumbency and upright posture in black males. Such differences were not seen in age-matched white subjects. Stimulation of the sympathetic nervous system by upright posture increased both Vne and Ane in all subjects. NE concentrations in simultaneously obtained arterial and venous samples were different during the time of cardiovascular adjustments to upright posture. The urinary Xne increased after standing. Endogenous CCr decreased, whereas apparent NE clearance, calculated from the Ane, increased after standing, suggesting that a major portion of the augmented urinary Xne induced by upright posture was from an intrarenal source. We conclude that the concentration of NE in human blood is related to the specific vascular bed from which the sample is obtained, and that urinary NE is not solely derived from plasma by glomerular filtration but also arises from an unidentified renal source.

Adult↗
PubMed1979

Diagnosis and localization of pheochromocytoma. Detection by measurement of urinary norepinephrine excretion during sleep, plasma norepinephrine concentration and computerized axial tomography (CT-scan).

The feasibility of differentiating patients with pheochromocytoma from other hypertensive patients by measuring urinary excretion rates of norepinephrine during sleep, a period of physiologic suppression of norepinephrine release, was investigated. The mean excretion rates of norepinephrine in 248 normal subjects and in 109 patients with essential hypertension were 1.03 +/- 0.03 and 1.12 +/- 0.06 (SEM) micrograms/hour, respectively, whereas the lowest excretion rate among the six patients with pheochromocytoma was about seven times higher. Plasma norepinephrine concentration in patients with pheochromocytoma was also consistently above the range observed in both normotensive and hypertensive subjects. CT scan correctly identified the same tumors visualized by selective arteriography. It is suggested that the usefulness of these approaches will provide simpler means of screening and detecting pheochromocytoma.

Adolescent↗
PubMed1975

Nerve stimulation-meditated overflow of norepinephrine and dopamine-beta-hydroxylase. III. Effects of norepinephrine depletion on the alpha presynaptic regulation of release.

A frequency-dependent increase in the overflow of norepinephrine (NE), 3-H-NE, total 3-H and dopamine-beta-hydroxylase (DBH) activity per nerve impulse was obtained after electrical stimulation of the isolated, perfused cat spleen. Over the range of frequencies studied, a proportional increase in the overflow of transmitter and DBH activity was observed, suggesting that an increase in the exocytotic release of NE is the primary mechanism by which the overflow of transmitter is enhanced with increasing frequencies of stimulation. The effects of 3 muM phenoxybenzamine (PBA) on the nerve stimulation-mediated overflow of NE, total 3-h, 3-h-ne and DBH activity were studied at two frequencies of stimulation, 1 and 5 Hz, in spleens from control and alpha-methyl-p-tyrosine-treated cats. Similarly, release of DBH activity was studied in spleens of reserpine-treated cats. In spleens from control cats, PBA produced a marked increase in the overflow of transmitter and DBH activity. This enhancement was more pronounced at 5 Hz than at 1 Hz. It was estimated that only 10 and 25% of the overflow of NE obtained in the presence of PBA at 1 and 5 Hz, respectively, could be accounted for by increased exocytosis. Depletion of tissue NE (80%) by pretreatment with alpha-methyl-p-tyrosine considerably reduced the effectiveness of PBA in enhancing the nerve stimulation-mediated overflow of NE, 3-H-NE, total 3-H and, particularly, of DBH activity. After reserpine treatment, the tissue NE content was reduced by more than 99%, yet the nerve stimulation-mediated release of DBH activity was similar to control spleens. PBA failed to enhance the nerve stimulation-mediated overflow of DBH activity after reserpine treatment. Thus it appears that the enhancement in the exocytotic release of transmitter by nerve stimulation observed in the presence of PBA is related to the concentration of NE in the synaptic space. Therefore, the present study is in favor of the notion that presynaptic alphareceptors may form part of a negative feedback control mechanism by which the transmitter may inhibit its own release.

Animals↗
PubMed1978

Relationship of basal plasma norepinephrine to blood pressure, plasma renin activity, mineralocorticoids, and plasma volume in essential hypertension.

The basal levels of plasma norepinephrine have been measured in 113 carefully characterized patients with essential hypertension, and the results have been correlated with the PRA sub-grouping and the levels of blood pressure, plasma aldosterone, plasma 18-hydroxy-deoxycorticosterone, and plasma volume. In addition, the influence of furosemide on plasma norepinephrine concentration has been assessed. Essential hypertensives, when considered as a whole, did not exhibit any significant abnormality in basal plasma norepinephrine concentration, but interesting alterations were observed in certain specific sub-groups. High renin patients had significantly elevated levels of basal plasma norepinephrine. In addition, a sub-group of the low renin population who were relatively young had reduced plasma norepinephrine conentration. In these individuals with both reduced PRA and plasma norepinephrine, the levels of both increased concomitantly to the normal range with marked salt depletion. Furosemide administration induced increases in plasma norepinephrine in all PRA sub-groups. Plasma norepinephrine correlated significantly with blood pressure in normal and low renin hypertensives, but the relationships were confined only to male subjects. Significant correlations were also observed between plasma norepinephrine and plasma aldosterine in males with normal PRA but not in the other sub-categories. No significant relationships between plasma volume and either plasma norepinephrine or blood pressure could be detected. Plasma 18-hydroxy-deoxycorticosterone was greater in males as compared with females and appeared elevated above control levels in normal and high renin essential hypertensives. Significant positive correlations between plasma aldosterone and plasma 18-hydroxy-deoxycorticosterone were observed in both males and females with normal renin hypertension. These studies have demonstrated abnormalities in basal plasma norepinephrine concentration in certain patients with essential hypertension. They also suggest that the levels of blood pressure and plasma aldosterone may be related to peripheral sympathetic activity in essential hypertension.

18-Hydroxydesoxycorticosterone↗
PubMedDate not supplied

Norepinephrine, potassium and overdrive suppression.

The influence of norepinephrine on ventricular overdrive suppression and attendant potassium shifts has been studied in isolated perfused canine hearts with complete atrioventricular block. It was found that: 1) there is a potassium loss during the drive and a potassium uptake after the drive); 2) reducing the driving rate from 240 to 120/min decreases potassium loss; 3) norepinephrine increases potassium uptake and spontaneously beating ventricles and during the recovery from 120/min drive; 4) norepinephrine enhances K loss during and after a 240/min drive; 5) norepinephrine shortens the overdrive pause under all the conditions tested; 6) in ventricles driven at a constant rate, norepinephrine causes a small loss of ptoassium; 7) reserpinized hearts show a small potassium loss during drive and a larger potassium uptake after drive; yet, the suppression is longer; 8) norepinephrine increases K loss with drive and decreases overdrive suppression in reserpinized hearts; 9) norepinephrine enhances the increase in oxygen consumption caused by overdrive; and 10) norepinephrine antagonizes the depressant effect of high [K]0 on automaticity. It is concluded that norepinephrine shortens the pause independently of potassium levels and antagonizes the inhibittory influence of high K. The effect or norepinephrine on K movements depends on the ventricular rate and such rate-dependence is related to oxygen availability with respect to the increased metabolic demand.

Animals↗
PubMed1979

Stereospecific (--)-[3H]norepinephrine binding to bovine hypothalamus. Possible identification of the catecholamine uptake site in synaptic vesicles.

A (--)-[3H]norepinephrine binding site was identified in a crude synaptosomal fraction isolated from bovine hypothalamus which bound norepinephrine rapidly, reversibly, and stereospecificially. The results were most consistent with binding of (-)-[H]norepinephrine to the carrier molecule used to translocate biogenic amines into synaptic vesicles. The binding studies indicated that specific binding of (--)-[3H]norepinephrine to the crude synaptosomal fraction was greatly enhanced by 4 mM MgCl2 pand 1 mM ATP. The increased binding of (--)-[3H5norepinephrine also occurred in the presence of MgCl2 and GTP, but AMP, adenosine and adenyl-5'-yl imidodiphosphate would not substitute for ATP. Neither CaCl2 nor ZnSO4 could be substituted for the MgCl2. In the presence of MgCl2 and ATP, the dissociation constant for (--)-[3H]norepinephrine was 280 nM with a specific binding site density of 4.8 pmol/mg protein. Binding was stereospecific with ratios of 15, 4, and 6.5 for the affinities of (--)-isomers to (+)-isomers for norepinephrine, epinephrine and isoproterenol, respectively. Drug competition studies, conducted in the presence of Mg2+ and ATP, indicated that (--)-epinephrine, (--)-norepinephrine, dopamine and serotonin had inhibitory constants ranging from 0.25 to 0.8 micron with (--)-isoproterenol and tyramine having inhibitory constants around 2 micron. Reserpine was the most potent inhibitor having an inhibition constant of 8.6 +/- 0.3 nM. The binding data were not consistent with the specific site being the alpha- or beta-receptors for norepinephrine, the Uptake1 Site for norepinephrine into synaptosomes or the metabolizing enzymes for norepinephrine.

Adenine Nucleotides↗
PubMed1978

Norepinephrine: hormone and neurotransmitter in man.

To determine whether norepinephrine could subserve a hormonal as well as a neurotransmitter function, norepinephrine was infused for 60 min into each of five normal young men in doses of 0.1, 0.5, 1.0, 2.5, and 5.0 microgram/min. After infusion, the plasma norepinephrine concentration fell with a mean (+/-SD) half-time of 2.4 +/- 0.7 min. The mean (+/-SD) norepinephrine metabolic clearance rate was 3,070 +/- 200 ml/min. The calculated basal plasma norepinephrine production rate was 0.7 microgram/min. The blood pressure and circulating glycerol, acetoacetate, beta-hydroxybutyrate, and glucose (increased) and the heart rate and circulating insulin, lactate, pyruvate, and alanine (decreased) exhibited highly significant parabolic relationships with the steady-state plasma norepinephrine concentrations. However, norepinephrine levels in excess of 1,800 pg/ml were required to produce hemodynamic and/or metabolic effects. Thus, under usual conditions, the biologic actions of norepinephrine can be attributed only to its sympathetic neurotransmitter function. Plasma norepinephrine concentrations do at times exceed 1,800 pg/ml during exercise and during major acute illness. Thus, under conditions of stress, norepinephrine may subserve a hormonal, as well as a neurotransmitter, function.

Adult↗
PubMed1975

Effects of 6-hydroxydopamine and reserpine on amphetamine-induced release of norepinephrine in rat cerebral cortex.

Amphetamine released 3-H-norepinephrine from rat cerebral cortex tissue which had previously accumulated the 3-H-amine. Destruction of noradrenergic nerve endings by pretreatment of the rats with 6-hydroxydopamine inhibited the accumulation of 3-H-norepinephrine by the tissue and reduced the proportion of the 3-H-amine which was released by amphetamine. Inhibition of storage of 3-H-norepinephrine within nerve endings by pretreatment of the animals with reserpine also reduced accumulation of 3-H-norepinephrine but did not reduce the proportion of the accumulated 3-H-amine which was released by amphetamine. The addition of desipramine (an inhibitor of neuronal uptake) further reduced the accumulation of 3-H-norepinephrine in animals pretreated with reserpine but had no further effect in animals pretreated with 6-hydroxydopamine. A greater proportion of the 3-H-norepinephrine was converted to 3-H-deaminated metabolites in tissues of reserpine-treated animals than in the tissues of control or 6-hydroxydopamine-treated rats. Amphetamine-induced release of 3-H-norepinephrine was partially calcium dependent in tissues from control animals. After reserpine treatment, amphetamine-induced release of norepinephrine was independent of calcium, whereas potassium-mediated release was still markedly calcium dependent. These experiments indicate that amphetamine releases 3-H-norepinephrine primarily from storage sites within central adrenergic nerve endings. An analysis of the time course of release from tissues of rats treated with reserpine suggests that amphetamine is equally capable of releasing 3-H-norepinephrine from granular sites which are susceptible to reserpine and from reserpine-insensitive sites.

Amphetamine↗
PubMed1976

Inhibition by acetylcholine of the norepinephrine release evoked by potassium in canine saphenous veins.

In the dog's saphenous vein acetylcholine inhibits the norepinephrine release caused by nerve stimulation, but not that caused by tyramine. Experiments were performed to determine whether acetylcholine affects the release of norepinephrine evoked by high K+ concentrations. We recorded changes in isometric tension of dog saphenous vein strips. Acetylcholine (5 X 10(-9) to 10(-6) g/ml) caused dose-dependent relaxations during contractions caused by K+ = 40 mEq/liter. These relaxations were not depressed by tetrodotoxin (10(-7) g/ml), which abolished the response to nerve stimulation, but were inhibited by atropine (10(-7) g/ml). Strips of saphenous veins were incubated with [3H]norepinephrine and mounted for superfusion (3 ml/min) and isometric tension recording; the total radioactivity and the amount of intact [3H]norepinephrine present in the superfusate were determined. K+ at 50 mEq/liter increased tension, total radioactivity of the superfusate, and the [3H]norepinephrine afflux; acetylocholine (10(-7) g/ml) depressed the contractions and diminished the efflux of [3H]norepinephrine. Increasing the K+ concentration from 50 to 70 mEq/liter augmented both tension and the evoked release of [3H]norepinephrine. Acetylcholine did not significantly alter the release of [3H]norepinephrine evoked by K+ = 120mEq/liter. These experiments show that acetylcholine inhibits the norepinephrine release evoked by potassium ions, as it does during nerve stimulation. The inhibition of adrenergic neurotransmission is not due to interference with action potential electrogenesis, but probably is caused by hyperpolarization of the adrenergic nerve endings.

Acetylcholine↗
PubMed1979

Possible role of brain norepinephrine in the hypothalamic hypophyseal adrenal system.

Intracisternal injection of bethanidine in rats decreased brain norepinephrine turnover without affecting its endogenous level, and increased both cardiac norepinephrine turnover and serum corticosterone level. A negative correlation was observed between brain norepinephrine turnover rate and serum corticosterone level. On the other hand, when cardiac norepinephrine turnover was suppressed by intraperitoneal injection of bethanidine, serum corticosterone did not change significantly. Next, ether inhalation was added after intracisternal injection of bethanidine. Then, serum corticosterone increased more even brain norepinephrine turnover was suppressed only slightly. These data may indicate that serum corticosterone increases by selective decrease in brain norepinephrine turnover via the humoral route; from the hypothalamus down to the adrenal cortex. Inversely, intracisternal injection of corticosterone increased brain norepinephrine turnover. These results suggest that brain norepinephrine may play an inhibitory role in the tonic regulation of CRF-ACTH secretion in the higher center than the hypothalamus and there may be a closed-loop feedback system between brain norepinephrine and serum corticosterone.

Animals↗
PubMed1975

Interaction of angiotensin with exogenous and neurally released norepinephrine on the cat nictitating membrane in vitro.

We have studied the effect of high (1-2.9 X 10(-5) M) and low 1.9 X 10(-9) M) concentrations of angiotensin on the retention and release of 3H-norepinephrine by the cat isolated nicititating membrane preparation in vitro in conjunction with their effect on the contractile responsiveness of the preparation to exogenous norepinephrine and transmural electrical stimulation. Both concentrations of angiotensin made the preparation contract, but only the high concentration affected the retention and spontaneous efflux of 3-H-norepinephrine. Retention was inhibited about 25% only when the preparation was preincubated with the angiotensin for 30 minutes (i.e., before adding 3H-norepinephrine). Under similar conditions cocaine, 2.9 X 10(-5) M, inhibited retention more than 90%. Spontaneous efflux was increased for as long as the high concentration of angiotensin was in contact with the preparation. Under similar conditions, tyramine, 5.7 X 10(-6) M, caused a much greater sustained increase in spontaneous efflux. Transmural stimulation of the preparation caused release of 3H-norepinephrine and frequency-dependent contractions. The contractions were selectively inhibited by phentolamine, 2.7 X 10(-6) M, or bretylium, 2.4 X 10(-5) M. Angiotensin had no effect on this neurally mediated 3H-norepinephrine release and contractile response or on contractions produced by exogenous norepinephrine. Since, as reported previously, angiotensin in vivo strongly inhibits contractile responses of the cat nicitating membrane to both neurally released and exogenous norepinephrine, the present results make it unlikely that such inhibition derives from angiotensin's relatively modest capacity for affecting the disposition of norepinephrine by this effector organ.

Angiotensin II↗
PubMed1978

alpha- and beta-receptor blockade of isoproterenol- and norepinephrine-induced effects on regional blood flow and blood flow acceleration.

The effects of the beta-receptor blocking agent propranolol (100 microgram/kg i.v.) and of the alpha-receptor blocking agent dihydroergotamine (50 microgram/kg i.v.) on hemodynamic responses to isoproterenol and norepinephrine (both 1--1024 ng/kg) were investigated in anesthetized dogs. The effects studied were: (1) flow in the ascending aorta and the coronary, common hepatic, gastroduodenal, splenic, cranial mesenteric, renal and femoral arteries: (2) maximal flow acceleration in the splenic, cranial mesenteric and femoral arteries; (3) maximal rate of change of left ventricular pressure (LV dP/dt max). Propranolol shifted the dose-response curves for the isoproterenol-induced flow increases in the common hepatic, gastro-duodenal, and cranial mesenteric arteries to the right. It did not influence the flow responses to isoproterenol in the ascending aorta or the coronary, splenic, renal and femoral arteries. Propranolol prevented the decrease of arterial pressure evoked by isoproterenol. Propranolol shifted the isoproterenol-induced increase of LV dP/dt max and maximal blood flow to the same extent. Propranolol blocked the flow to the liver and gastrointestinal tract to a greater extent than the LV dP/dt max and maximal flow acceleration. Propranolol had no effect on the norepinephrine-induced increases in flow in the splenic, femoral and coronary arteries, but blocked the norepinephrine-evoked increases of flow accelerations and LV dP/dt max to the same extent. Dihydroergotamine inhibited the norepinephrine-induced increase in flow in the femoral artery and the decreases in flow in the hepatic, splenic, cranial mesenteric and renal arteries, and reversed the reduction of flow in the gastroduodenal artery. It is argued that dihydroergotamine may inhibit the increase in femoral flow through two mechanisms: (1) blocking the flow reduction to norepinephrine in the abdomen, and thereby passively shunting blood from the abdomen in preference to the femoral bed; (2) attenuating the norepinephrine-evoked reflexogenic femoral vasodilatation. It is concluded that: (1) propranolol is a beta-receptor blocking agent with a preference for blockade of isoproterenol-induced vascular effects; (2) norepinephrine-induced flow increases are not direct actions on vascular beta-receptors; (3) the increase of maximal blood flow accelerations after isoproterenol and norepinephrine is mediated by stimulation of cardiac beta-receptors; (4) dihydroergotamine is an alpha-receptor blocking agent particularly in the splanchnic vascular region.

Adrenergic alpha-Antagonists↗
PubMed1977

Central and peripheral norepinephrine metabolism in rat strains selectively bred for differences in response to stress.

Rats of the Maudsley nonreactive (MNRA) strain were found to contain higher levels of norepinephrine in heart, spleen, and hypothalamus than animals of the Maudsley reactive (MR) strain. Total adrenal catecholamines were also greater in nonreactive animals. There was a trend toward higher endogenous norepinephrine concentration in MR rats in brainstem and telencephalon, but this was not statistically significant. Turnover measurements calculated from the fall of norepinephrine at 1 and 4 hours after a single dose of levo-alpha-methylparatyrosine showed no significant strain differences in telencephalon or brainstem, but MNRA animals had a faster rate of norepinephrine decline in heart than had MR rats. Possibly indicative of a higher rate of norepinephrine metabolism, the percentage of 3H-non-catechol metabolites relative to total counts was higher in brainstem of MNRA rats 90 min after intraventricular injection of 3H-norepinephrine. However, the disagreement between this estimate of norepinephrine metabolism and that provided by the alpha-methyl-paratyrosine technique prevents a conclusive statement about norepinephrine metabolism in the two strains. The results are discussed in the light of the established differences in behavior between the strains as well as other work exploring relationships between catecholamine metabolism and emotionality.

Adrenal Glands↗
PubMed1975

Interactions of 17beta-estradiol and L-norepinephrine on the rat uterus.

Norepinephrine increased the in vitro uptake of 3H-estradiol by the uterus of spayed rats. This effect was observed at 15 and 30 min but not at 90 min. Norepinephrine also increased the binding of 3H-estradiol by the nuclear (p less than 0.02) and the cytosol fractions (p less than 0.01) when incubated with uterine homogenates, suggesting that norepinephrine does not require the presence of the intact tissue to exert its effects. The in vivo uptake of 3H-estradiol and the determination of the number of binding sites were performed in the uterus of rats treated with estradiol and estradiol plus norepinephrine. Norepinephrine alone increased the uptake of 3H-estradiol and the number of binding sites. The highest increment in both parameters was observed in the uterus of rats treated with estradiol plus norepinephrine. The estradiol Ka of the rat uterus cytosol treated with estradiol alone or plus norepinephrine was higher than that observed in the group without estradiol, suggesting the presence of different proteins that bind estradiol. These results indicate that norepinephrine increases the entrance of estradiol into the rat uterus both in vitro and in vivo.

Animals↗