Increase In Plasma Norepinephrine Concentration Research Articles

Activation of the Renin-Angiotensin System by Sodium Nitroprusside in Essential Hypertension

We previously have demonstrated that the sympathetic nervous system is activated proportionately to the degree of vasodepression induced in hypertensive patients. In the present study, the role of the renin-angiotensin system in modulating the vasodepressor response to sodium nitroprusside was examined. Nine hospitalized hypertensive patients receiving a diuretic were given serially incremental doses of sodium nitroprusside over a dose range of 0.05-4.8 micrograms/kg/min with each dose being infused for 10 min. Mean arterial pressure (MAP), heart rate (HR), plasma renin activity (PRA), and plasma norepinephrine (NE) concentration were measured prior to and during each dose level of sodium nitroprusside. Stepwise increments in PRA were seen in each patient as the dose of sodium nitroprusside was increased. The increase in PRA was proportional to the increase in plasma NE concentration and to the decrease in MAP in each patient. However, considerable intersubject variation was seen in these relationships. When examined by multiple linear stepwise regression analysis, the degree of vasodepression was found to be dependent on the baseline blood pressure and baroreflex sensitivity (r = 0.97). However, increment in PRA was not an independent determinant of the vasodepressor response. Thus, the renin angiotensin system may not be a significant component of the acute homeostatic response to vasodepression in these patients.

Central and regional hemodynamic effects and neurohumoral consequences of minoxidil in severe congestive heart failure and comparison to hydralazine and nitroprusside

Minoxidil is a potent oral vasodilator of potential value in patients with congestive heart failure (CHF), although preliminary studies show that it causes fluid retention. To test whether minoxidil acts primarily as an arterial vasodilator in CHF, it was compared with hydralazine and nitroprusside. To evaluate its chronic efficacy and mechanism of fluid retention, the effects of minoxidil (7 patients) were compared, in a double-blind manner, with those of hydralazine (8 patients) on central and regional hemodynamics and the renin-angiotensin-aldosterone and sympathetic nervous systems. There was no demonstrable difference in the central hemodynamic effects of minoxidil and hydralazine in the dosages used. After 6 hours both drugs increased cardiac index (minoxidil group, from 1.65 ± 0.29 to 2.26 ± 0.40 liters /min/m 2, p < 0.0001; hydralazine group, from 1.88 ± 0.61 to 2.34 ± 0.90 liters/min/m 2, p < 0.0001), decreased systemic vascular resistance and increased heart rate without change in pulmonary arterial, pulmonary capillary wedge or right atrial pressures. Nitroprusside effects differed from those of minoxidil and hydralazine with respect to heart rate (p < 0.005) and mean pulmonary arterial (p < 0.007) and right atrial (p < 0.009) pressures. Nitroprusside also decreased relative hepatomesenteric flow compared with the other 2 agents (p < 0.005). Neither renal blood flow, glomerular filtration rate, filtration fraction, nor urinary sodium excretion were significantly altered acutely by any of the 3 drugs. Minoxidil and hydralazine did not differ in their neurohumoral effects: Both agents produced an increase in plasma norepinephrine concentration (p < 0.003) and plasma renin activity (p < 0.04), but no change in plasma epinephrine or aldosterone concentrations. After 1 week of double-blind therapy, fluid retention was a greater problem with minoxidil than with hydralazine. Thus, minoxidil behaves primarily as an arterial vasodilator in CHF, fluid retention is a severe adverse effect, and the greater degree of fluid retention with minoxidil than hydralazine is not attributable to differing acute effects on total renal blood flow or function, or differing effects on the renin-angiotensin-aldosterone or sympathetic nervous systems.

Assessing the noradrenergic system in normal aging: a review of methodology.

Studies evaluating plasma norepinephrine in the normal elderly have found significant increases as compared to the young and middle-aged individuals. The increased plasma norepinephrine concentrations found during the normal aging process in man may be relevant to both the understanding of drug therapeutics and underlying mechanisms of the noradrenergic system in the elderly. The authors critically review the experimental design of studies that have evaluated plasma norepinephrine and age. The various conditions and methods for assessment of plasma norepinephrine concentrations, which may contribute to the finding of a hypernoradrenergic system in the aged, are examined. An attempt is made to collate the studies and develop a standardized methodology for studying the peripheral noradrenergic system in the elderly.

Is there a relationship between gastric acid secretion and plasma catecholamines in duodenal ulcer disease?

Plasma adrenaline, noradrenaline and dopamine concentrations have been analyzed in three different groups of duodenal ulcer (DU) patients under various regimens of acid reduction in an attempt to find out if acidity per se has any influence on plasma catecholamine concentrations. Treatment with cimetidine in patients with asymptomatic chronic DU disease, reduced gastric acidity to the same level as after highly selective vagotomy (HSV), but increased plasma noradrenaline concentrations insignificantly. In a group of DU patients subjected to HSV, plasma noradrenaline levels were significantly higher 1 year after surgery than 6 weeks thereafter despite the fact that the basal acid output was the same. In a third group of DU patients, plasma noradrenaline and dopamine levels were found to be 20% higher during the active, untreated ulceration than after 4 weeks of ranitidine treatment when the ulcer had healed. It is concluded that the elevated plasma noradrenaline levels found in DU patients are not caused by the hypersecretion of acid per se, nor does there seem to be any general correlation between acidity and the catecholamine levels in peripheral plasma.

Renal alpha-adrenergic receptor abnormality in the spontaneously hypertensive rat.

Activation of renal alpha-adrenergic receptors induces vasoconstriction, proximal tubular reabsorption of sodium, and inhibition of renal release. Excesses of these effects are present in varying degrees in animal models of, and in patients with, "essential" hypertension. Since essential hypertension is genetically determined, we sought abnormalities of renal alpha-adrenergic receptors in the Okamoto-Aoki strain of spontaneously hypertensive rats (sr-SHR) and their stroke-prone variant (sp-SHR). Total alpha-adrenergic receptor concentrations were determined by Scatchard analysis of [3H]dihydroergocryptine binding to a renal membrane fraction and were found to be increased (p less than 0.02) in male sr-SHR at 4, 16, and 32 weeks of age and in female sr-SHR at 16 weeks of age as compared to age- and sex-matched Wistar-Kyoto controls. They were also increased in 9-week-old sp-SHR renal membranes (p less than 0.005). Further studies revealed that this increase in renal alpha-adrenergic receptors was due entirely to an increase in alpha 2-receptors as measured by [3H]yohimbine binding rather than to an increase in alpha 1-receptors as quantitated by [3H]prazosin binding. No difference in binding affinities of the various radioligands could be demonstrated between any of the hypertensive and normotensive groups of rats. Plasma norepinephrine levels were elevated (p less than 0.01) in the 4-, 9- and 16-week-old SHR, but not in the 32-week-old hypertensive rats. Thus, high renal alpha 2-adrenergic receptor number is coupled with a significant increase in plasma norepinephrine concentrations during the development of hypertension in SHR. By mediating an enhanced receptor-coupled response, such as increased proximal tubular sodium reabsorption, this abnormality of renal alpha-adrenergic receptors may contribute to some or all of the pathophysiologic derangements leading to hypertension in SHR.

Effects of food on plasma catecholamine and gastrin levels in patients with duodenal ulcer and normal volunteers.

Changes in plasma concentrations of adrenaline, noradrenaline, dopamine and gastrin in response to a standard meal were studied in 6 normal volunteers and 8 patients with chronic duodenal ulcer (DU) disease. Before the meal plasma gastrin and noradrenaline, but not adrenaline or dopamine, were higher in DU patients than in the controls. Food induced significant increments in plasma gastrin and noradrenaline concentration in both groups, whereas plasma adrenaline and dopamine levels remained unchanged. Plasma gastrin and noradrenaline concentrations were higher in DU patients than in the normal controls both during and after the meal. The results do not support the hypothesis that adrenaline is involved in the pathogenesis of duodenal ulcer disease, whereas the role of the increased plasma noradrenaline concentrations in this disease remains unclear.

Hemodynamics in diabetic orthostatic hypotension.

Hemodynamic variables (blood pressure, cardiac output, heart rate, plasma volume, splanchnic blood flow, and peripheral subcutaneous blood flow) and plasma concentrations of norepinephrine, epinephrine, and renin were measured in the supine position and after 30 min of quiet standing. This was done in normal subjects (n = 7) and in juvenile-onset diabetic patients without neuropathy (n = 8), with slight neuropathy (decreased beat-to-beat variation in heart rate during hyperventilation) (n = 8), and with severe neuropathy including orthostatic hypotension (n = 7). Blood pressure decreased precipitously in the standing position in the diabetics with orthostatic hypotension, whereas moderate decreases were found in the other three groups. Upon standing, heart rate rose and cardiac output and plasma volume decreased similarly in the four groups. The increases in total peripheral resistance, splanchnic vascular resistance and subcutaneous vascular resistance were all significantly lower (P less than 0.025) in the patients with orthostatic hypotension compared with the other three groups. The increase in plasma norepinephrine concentrations in the patients with orthostatic hypotension was significantly lower (P less than 0.025) than in the patients without neuropathy, whereas plasma renin responses to standing were similar in the four groups. We conclude that in diabetic hypoadrenergic orthostatic hypotension the basic pathophysiological defect is lack of ability to increase vascular resistance, probably due to impaired sympathetic activity in the autonomic nerves innervating resistance vessels; cardiac output and plasma volume responses to standing are similar to those found in normal subjects and in diabetics without neuropathy.

Rat (Ile5) but not bovine (Val5) angiotensin raises plasma norepinephrine in rats.

A part of the vasoconstrictor activity of angiotensin II (AII) may result from its ability to enhance norepinephrine (NE) release from sympathetic noradrenergic nerve terminals. To investigate this proposed pressor mechanism of AII, the effects of intravenous (i.v.) infusion of AII on blood pressure and plasma catecholamines in pithed rats were determined. Two naturally occurring angiotensins, valine5 AII (bovine) and isoleucine5 AII (rat), were administered in equal (72 ng/min) doses. Valine5 AII caused an 80% increase in mean arterial pressure (MAP) from 54 +/- 4 to 97 +/- 19 mm Hg. Isoleucine5 AII caused an 82% increase in MAP from 49 +/- 5 to 89 +/- 18 mm Hg. Neither angiotensin caused a change in heart rate, suggesting that pithing completely destroyed the central baroreceptor reflex mechanism. Plasma catecholamines were differentially affected by the peptides:isoleucine5 AII significantly increased plasma NE concentration by 82% compared to saline-infused rats (p less than 0.01). Valine5 AII did not significantly affect plasma NE concentration. Plasma dopamine and epinephrine concentrations were not significantly altered by infusion of either analog. Despite the significant increases in plasma NE concentrations with isoleucine5 in AII-infusion rats, there was no correlation between plateau MAP or the percent increase in MAP and plasma NE concentrations of individual animals within this group. The ability of angiotensin to elevate MAP, increase NE release from sympathetic nerve terminals, as well as potential differences in the actions of angiotensins in different species, and angiotensin receptor heterogeneity, are discussed.

Prolonged clonidine treatment: catecholamines, renin activity and aldosterone following exercise in hypertensives.

Eight patients with essential hypertension, WHO grade I-III, were studied under standardized conditions in a metabolic ward, before and after 8-20 weeks of treatment with clonidine in a maintenance dose of 300-600 micrograms/24 h. Before clonidine, plasma noradrenaline concentration (PNA), plasma adrenaline concentration (PA), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) increased in response to standing and submaximal exercise for 20 min. PNA was positively correlated to pulse rate in the supine position (R = 0.74, p 0.05) and the increase in PNA to the increase in pulse rate during exercise (min 10, R=0.73, p less than 0.05; min 15, R = 0.79, p less than 0.05; min 20, R = 0.74, p less than 0.05). No other significant correlations were found between PNA, PA, PRA and PAC on the one hand and blood pressure (BP) and pulse rate on the other. Clonidine reduced BP, pulse rate, PNA and PRA under all conditions studied. PA was reduced in the upright position and in connection with exercise. PAC was reduced during clonidine after exercise but otherwise unaltered. The clonidine-induced decrease in PNA was positively correlated to the decrease in diastolic BP both in the supine (R = 0.76, p less than 0.05) and in the upright (R = 0.80, p less than 0.05) position. thus, long-term clonidine treatment lowered the BP and pulse rate, at least partly by reducing sympathetic activity via a central mechanism. However, clonidine did not block the sympathetic reflex mechanisms engaged in the maintenance of BP in the upright position. During clonidine, the adrenaline values were lower than before treatment in the supine and in the upright position and also following exercise, indicating that clonidine exerts an inhibitory effect on the sympatho-adreno-medullary system.

Effects of abrupt cessation of treatment with clonidine and guanfacine on blood pressure and heart rate in spontaneously hypertensive rats.

Present experiments were undertaken to compare the effects of clonidine and guanfacine withdrawal on blood pressure in spontaneously hypertensive rats. Five week oral administration of clonidine at a dose of approximately 300 microgram/kg/day produced a significant hypotension. After acute interruption of clonidine administration, a marked blood pressure rise was observed. Peak blood pressure rise was reached within 24 hours after clonidine withdrawal. A significant increase in plasma norepinephrine concentration was observed when clonidine treatment was discontinued. On the other hand, long-term administration of guanfacine at a dose of approximately 3 mg/kg/day produced a significant hypotension. After a five week administration of guanfacine, abrupt cessation did not produce a rapid blood pressure rise. Catecholamine concentration in urine and plasma was not influenced either by guanfacine administration or its withdrawal.

Enhanced sympathetic activity caused by salt loading in spontaneously hypertensive rats.

1. Salt loading accelerates and increases the rise in blood pressure (spSH) in stroke-prone spontaneously hypertensive rats, but not in Wistar-Kyoto (WK) rats. 2. In both strains a slight increase in plasma volume was obtained during salt loading. 3. Salt loading caused a distinct increase in plasma noradrenaline concentration in spSH rats, but a slight decrease in WK rats. Plasma adrenaline and dopamine concentrations remained unaffected. 4. Exposure to cold resulted in a more marked stimulation of sympathoadrenal and sympathoneuronal activity in salt-loaded spSH rats than in spSH rats on a normal sodium diet. 5. It is concluded that salt loading results in a further increase of the already elevated sympathetic activity in spSH rats.

Increased plasma norepinephrine concentrations and metabolic rates following glucose ingestion in man

The effects of glucose ingestion on plasma levels of norepinephrine (NE), epinephrine (E), immunoreactive insulin (IRI), and glucose, and the resting metabolic rate (RMR) were examined in six normal males. Ingestion of the glucose (100 g) solution significantly increased all of these measures except E levels, compared with changes observed during a control experiment in which an equal volume of water was ingested. The initial (0–60 min) increase in plasma NE levels and the increase in the RMR following glucose was significantly greater than the smaller increases that occurred during the control experiment. Plasma IRI and glucose levels peaked 30–60 min after glucose consumption, then declined toward basal values. These data show that glucose intake causes an elevation of the RMR and sympathetic nervous system activity greater than that caused by other aspects of the testing solution, and are consistent with the possibility that the increase in RMR following glucose ingestion is related to elevated sympathetic nervous system activity.

Pharmacological evidence for a functional role of the prejunctional alpha-adrenoreceptor in noradrenergic neurotransmission in the conscious rat.

The functional role of the prejunctional alpha-adrenoreceptor was studied in normal, adrenalectomized and desmethylimipramine pretreated conscious rats. Alpha-adrenoreceptor antagonists with differing in vitro selectivities for the prejunctional alpha-adrenoreceptor were administered, and their effects on arterial blood pressure, heart rate and plasma noradrenaline concentration determined. Following prazosin, an alpha-receptor antagonist with selectivity for the postjunctional alpha-adrenoreceptor, plasma noradrenaline concentration increased to a level slightly above that attributable merely to reflex activation of the sympathetic nervous system by the direct-acting vasodilator, hydralazine. In contrast, administration of equipotent hypotensive doses of phenoxybenzamine and phentolamine, alpha-receptor antagonists which block both pre- and postjunctional alpha-adrenoreceptors, resulted in marked and sustained increases in plasma noradrenaline concentration. The increases in heart rate following these agents were proportional to the changes in noradrenaline. Yohimbine, an alpha-receptor antagonist with selectivity for the prejunctional alpha-adrenoreceptor, resulted in a modest and transient reduction in arterial blood pressure but a sustained increase in heart rate and a three-fold increase in plasma noradrenaline concentration. In addition, dose-response studies revealed that for a given reduction in arterial pressure, prazosin caused a lesser increment in plasma noradrenaline concentration and heart rate, than phentolamine. Studies in adrenalectomized rats and rats pretreated with desmethylimipramine excluded a direct effect on the adrenal medulla and blockade of the neuronal uptake process, respectively, as the mechanism for the observed increments in plasma noradrenaline concentration. As the spectrum of changes in plasma noradrenaline concentration and heart rate is consistent with the in vitro selectivities of these agents to block the prejunctional alpha-receptor, these findings provide evidence for a functional role of this receptor in noradrenergic neurotransmission in the rat.

Guanfacine in essential hypertension: effect on blood pressure, plasma noradrenaline concentration and plasma renin activity.

1. The acute and chronic effects of guanfacine on blood pressure, plasma noradrenaline concentration and plasma renin activity were investigated in 23 patients (15 males, 8 females) with essential hypertension (WHO grade I-II). 2. Guanfacine induced a decrease in plasma noradrenaline concentration and plasma renin activity concomitant with a fall in blood pressure and heart rate in both the acute and the chronic study. 3. The adrenergic response to upright posture, reflected by an increase in plasma noradrenaline concentration and plasma renin activity, was not abolished after chronic guanfacine therapy. 4. The decrease in blood pressure 15 min after intravenous administration of guanfacine was inversely correlated with the basal sympathetic activity before treatment and with the decrease in plasma noradrenaline. 5. After chronic treatment with guanfacine no significant correlation existed between blood pressure reduction and the concomitant changes in peripheral sympathetic and/or plasma renin activity. 6. Despite the lack of a close correlation it is suggested that the antihypertensive effect of guanfacine in patients with essential hypertension is at least partially mediated by an inhibition of the sympathetic nervous and plasma renin activity.

Plasma noradrenaline response to sustained handgrip in patients with essential hypertension.

The responses of plasma noradrenaline, arterial blood pressure, and heart rate to sustained handgrip at 30% maximal voluntary contraction were studied in untreated patients with essential hypertension and in healthy subjects of comparable age. There were no significant differences between these two groups in the intensity and duration of handgrip. Increases in heart rate and blood pressure induced by the effort were similar in hypertensive patients and normotensive control subjects, whereas the absolute levels of blood pressure were considerably higher in the patients. In the first 1-2 min of exercise the increases in plasma noradrenaline concentration were similar in both groups. Subsequently, plasma noradrenaline concentration tended to plateau in hypertensive patients while in control subjects it continued to increase. The elevation of plasma noradrenaline in the last minute of effort was, therefore, significantly smaller in hypertensive patients than in the control group.

Studies of experimental cervical spinal cord transection

Plasma concentrations of norepinephrine (NE) were measured by a radioenzymatic assay technique before and serially after laminectomy at the C-6 level in 14 anesthetized dogs. In half the animals, no further procedures were carried out (control group); in the other dogs, cervical cord transection was performed in addition to laminectomy (experimental group). Mean plasma NE levels were similar in both groups after laminectomy and before cord interruption. In the control group, NE levels increased gradually for 2 hours after the procedure. In the group with cord transection, however, NE rose immediately after transection to 267% of the baseline value, then fell to 25% of the plasma NE level in the control group at 30 minutes, 29% at 60 minutes, and 15% at 120 minutes. Cervical spinal cord transection, therefore, results in an abrupt but short-lived increase in plasma NE concentrations. These changes in plasma NE levels may explain, at least in part, the hemodynamic alterations and the acute central hemorrhagic necrosis that occur after high spinal cord trauma.

Alterations in Plasma Norepinephrine Concentration During Surgical Resection of Pheochromocytoma

Using a sensitive and specific radioenzymatic assay, the plasma norepinephrine (NE) concentration was measured in seven patients with pheochromocytoma, one patient with bilateral adrenal medullary hyperplasia, one patient with a retroperitoneal paraganglioma, and two patients undergoing bilateral adrenalectomies for palliation of metastatic breast carcinoma. Surgical manipulation of the pheochromocytomas resulted in striking increases in plasma NE concentration with concomitant increases in blood pressure. There were either small changes or no changes in the patients' plasma NE and blood pressure during resection of the normal adrenal glands, the adrenal glands with medullary hyperplasia, or the retroperitoneal paraganglioma. Plasma dopamine-beta-hydroxylase (DBH) was measured in one patient with pheochromocytomas and the patient with medullary hyperplasia. There was no change in plasma DBH in either patient, supporting the concept that exocytosis is not the primary mechanism for catecholamine secretion from pheochromocytomas. It was also noted that enflurane is an excellent general anesthetic for the resection of pheochromocytomas, and that sodium nitroprusside (rather than phentolamine) may be the agent of choice for the management of the hypertensive episodes that occur during surgical manipulation of pheochromocytomas.

Renin-angiotensin system inhibition in conscious dogs during acute hypoxemia. Effects on systemic hemodynamics, regional blood flows, and tissue metabolism.

The role of the renin-angiotensin system in mediating the circulatory and metabolic responses to hypoxia was studied in three groups of conscious dogs that were infused continuously with normal saline, teprotide (10 mug/kg per min), and saralasin (1 mug/kg per min), respectively. Hypoxia was produced by switching from breathing room air to 5 or 8% oxygen-nitrogen mixture. Plasma renin activity increased from 2.3+/-0.4 to 4.9+/-0.8 ng/ml per h during 8% oxygen breathing, and from 2.8+/-0.4 to 8.4+/-1.8 ng/ml per h during 5% oxygen breathing. As expected, cardiac output, heart rate, mean aortic blood pressure, and left ventricular dP/dt and dP/dt/P increased during both 5 and 8% oxygen breathing in the saline-treated dogs; greater increases occurred during the more severe hypoxia. Teprotide and saralasin infusion diminished the hemodynamic responses to 5% oxygen breathing, but did not affect the responses to 8% oxygen breathing significantly. In addition, the increased blood flows to the myocardium, kidneys, adrenals, brain, intercostal muscle, and diaphragm that usually occur during 5% oxygen breathing were reduced by both agents. These agents also reduced the increases in plasma norepinephrine concentration during 5% oxygen breathing, but had no effects on tissue aerobic or anaerobic metabolism. In dogs pretreated with propranolol and phentolamine, administration of teprotide (0.5 mg/kg) during 5% oxygen breathing reduced mean aortic blood pressure and total peripheral vascular resistance, and increased cardiac output and heart rate, but did not affect left ventricular dP/dt, dP/dt/P, and end-diastolic pressure. Simultaneously, renal and myocardial blood flows increased and myocardial oxygen extraction decreased, while myocardial oxygen consumption did not change significantly. These results suggest that the renin-angiotensin system plays an important role in the hemodynamic responses to severe hypoxia. It appears that angiotensin not only exerts a direct vasoconstrictor action, especially upon the coronary and renal circulations, but also potentiates the cardiovascular effects of sympathetic stimulation that occur during severe hypoxia.

Sympathetic responsiveness and antihypertensive effect of beta-receptor blockade in essential hypertension

The relationship between sympathetic responsiveness and the blood pressure reduction induced by long-term beta-blockade was assessed in patients with essential hypertension. The increase in plasma noradrenaline concentration during physical exercise was used as an index of sympathetic responsiveness. The cardioselective beta-blocker, atenolol, was given to 16 patients with sustained benign essential hypertension for five weeks at a dose of 200 mg/day. Atenolol induced a marked decrease in blood pressure and pulse rate during recumbency, orthostasis and exercise concomitant with a marked increase in plasma noradrenaline concentration (p < 0.0125) and a pronounced decrease in plasma renin concentration (p < 0.01). The ratio of plasma noradrenaline during exercise to the base line concentration correlated significantly with the subsequent decrease in mean arterial blood pressure induced by beta-blockade (r = 0.840; p < 0.001). A less significant correlation was observed between the plasma renin concentration and the subsequent decrease in mean arterial pressure (r = 0.542; p < 0.05). The results obtained indicate that sympathetic responsiveness is an important determinant of blood pressure response to beta-blockade induced by atenolol.

Changes in plasma catecholamines and dopamine beta-hydroxylase after corrective surgery for coarctation of the aorta.

In six patients within 12 hours of surgical correction of aortic coarctation there was a 750% increase in plasma noradrenaline concentrations accompanied by an increase in systolic and diastolic blood pressures. The magnitude of the postoperative increase in noradrenaline concentrations was related to the preoperative level of the pressure gradient across the coarctation. Six months after operation plasma noradrenaline concentrations were still significantly elevated. In nine patients who underwent other types of major surgery there was a small increase in plasma noradrenaline concentrations and a return to levels within the normal range within 24 hours. Various explanations for the rise in plasma noradrenaline concentrations are considered. In particular the possibility is raised that after surgical correction of aortic coarctation the increased levels indicate a marked increase in sympathetic nervous system activity; this may be mediated by baroreceptor mechanisms and may persist for up to six months after surgery.