Plasma adrenaline and noradrenaline during mental stress and isometric exercise in man. The role of arterial sampling

Plasma adrenaline and noradrenaline were measured in arterial blood and in forearm venous blood during isometric exercise and during a mental stress test. In both conditions arterial plasma adrenaline increased significantly, whereas arterial plasma noradrenaline remained unchanged. During isometric exercise the increase in plasma adrenaline was greater in venous blood from the exercising arm than from the resting arm. The extraction of adrenaline in the forearm was greater in the resting than in the exercising arm. Venous plasma noradrenaline showed a rebound phenomenon after isometric exercise and tended to decrease during the mental stress test. The results indicate that it is preferable to measure arterial concentrations of adrenaline as an indicator of sympathoadrenal activity rather than venous concentrations since the extraction of adrenaline in forearm might not be constant. It is suggested that a selective increase in arterial plasma adrenaline as opposed to an increase in both plasma adrenaline and noradrenaline may indicate a selective increase in sympathoadrenal activity in visceral organs.     

Angiotensin II attenuates reflex decrease in heart rate and sympathetic activity in man

Summary. Circulatory variables and hormone concentrations in arterial plasma were measured in six normal subjects during angiotensin II (ANG II) step-up infusion of 0·25 and 1·00 ng kg^-1× min. During the 1·00 ng kg^-1× min infusion ANG II plasma concentrations increased from 11 ± 2 to 48 ± 6 pg ml^-1; i.e., similar to those obtained during acute hypotensive hypovolemia in man. Mean arterial pressure increased (P<0·05) from a resting value of 89±3 to 97±5 mmHg. Heart rate and catecholamine concentrations did not change. Plasma aldosterone increased (P<0·05) from 36 ± 4 to 77 ± 10 pg ml^-1 during the infusion. Plasma concentrations of vasopressin, adrenalin and pancreatic polypeptide did not change during the investigation. During the 0·25 and 1·00 ng kg^-1× min infusion subcutaneous blood flow decreased (P= 0·06) to 67 ±20 and 66 ±26%, respectively, of control. It is concluded that: (1) ANG II in physiological doses in man may augment the sympathetic activity on the circulatory system since compensatory decreases in heart rate or in plasma catecholamines were not observed during the increased arterial pressure; (2) ANG II does not induce a general decrease in vagal tone as plasma pancreatic polypeptide concentrations were unchanged; (3) the obtained plasma concentrations of ANG II do not stimulate the release of vasopressin to plasma; and (4) the threshold for reducing the subcutaneous blood flow is reached within relatively small increments in plasma ANG II.     

Different vascular responsiveness to angiotensin II in two normotensive rat strains

Rats of the Fischer 344 (F344) and Wistar Kyoto (WKY) strains are known to present differences in stimuli responses involving the renin-angiotensin system and in cardiovascular responses to an acoustic startle stimulus. Here we compared the vascular reactivity to angiotensin II (ANG II) of these normotensive, inbred rat strains. Blood pressure (BP) and heart rate (HR) were recorded in conscious rats, before and after a neurohumoral blockade obtained by successive administration of chlorisondamine, enalapril, a V1-vasopressinergic receptor antagonist (Manning compound) and atropine methyl nitrate. BP was restored by a constant infusion of noradrenaline. Boluses of ANG II ranging from 0.001 to 1280 ng/kg were injected randomly. Average dose-response curves were established. After neurohumoral blockade, the minimum mean BP (MBP) produced by hydralazine (3 mg/kg, i.v.) and the maximum MBP produced by noradrenaline (60 microg/mL and 800 microL/min, i.v.) were used to reflect arterial wall structure. The maximal systolic blood pressure (SBP) and pulse pressure (PP) responses to ANG II were higher in F344 compared with WKY (+86 +/- 3 mmHg vs. +71 +/- 3 mmHg, P < 0.01 for SBP, +31 +/- 2 mmHg vs. +18 +/- 1 mmHg, P < 0.001 for PP). After the ANG II type 1 (AT1) receptor blocker valsartan, ANG II had no significant effect on BP. F344 and WKY exhibited the same maximum MBP in response to noradrenaline. However, MBP level following hydralazine was higher in F344 (F344: 48 +/- 2 mmHg vs. WKY: 37 +/- 3 mmHg, P < 0.01). The amplification in F344 of the vasoconstrictive response to ANG II mediated by AT1 receptors is compatible with a high number of AT1 receptors in this strain. In F344, the exaggerated systolic and PP responses to ANG II and the higher MBP level after hydralazine most likely reflect a structural modification of the arterial wall such as hypertrophic remodelling in F344.     

Renal and hormonal actions of atrial natriuretic peptide during angiotensin II or noradrenaline infusion in man

In order to study the renal and hormonal actions of atrial natriuretic peptide (ANP) during background infusions with angiotensin II (ANG II) or noradrenaline (NA), 69 healthy subjects were examined in three main groups receiving a 90-min infusion with either placebo, ANG II (1.5 ng kg^?1 min^?1), or NA (25 ng kg^?1 min^?1). Each of these three main groups were subdivided into two groups receiving an infusion with either placebo or ANP (10 ng kg^?1 min^?1) for the last 60 min of the background infusion. Lithium clearance was used to evaluate segmental tubular reabsorption. ANG II alone caused a decrease in glomerular filtration rate (GFR), renal plasma flow, urinary absolute and fractional excretion of sodium, both proximal and distal fractional tubular sodium reabsorption, and urinary flow. NA alone caused a decrease in renal plasma flow. ANP alone caused a decrease in renal plasma flow. Urinary absolute and fractional excretion of sodium were increased and the distal fractional tubular reabsorption of sodium decreased, whereas the proximal fractional tubular reabsorption was unchanged by ANP. ANG II + ANP: during a background ANG II infusion, ANP still increased fractional excretion of sodium. Proximal fractional reabsorption was decreased, whereas distal fractional reabsorption of sodium was unchanged by ANP during ANG II infusion. The ANP-induced decreases in proximal absolute (?147 vs. +714 μmol min^?1 1.73 m^?2P = 0.05) and fractional (?1.7% vs. +0.6%, P<0.01) tubular sodium reabsorption were more pronounced, and the decrease in distal fractional tubular reabsorption of sodium (?0.1% vs. ?1.4%, P<0.05) less pronounced compared with when ANP was given alone. NA + ANP: during a background NA infusion, ANP still increased urinary sodium excretion and decreased distal fractional reabsorption. None of the ANP-induced absolute changes seen during background infusion with NA were significantly different from the ANP-induced changes seen during placebo background infusion. It is concluded that the natriuretic action of low-dose ANP seems to be preserved during background infusions with ANG II and NA in man. Net sodium excretion during the combined infusion with ANG II and ANP seems to reflect the sum of the opposing influences of each peptide. Low-dose ANP had a very modest but significant inhibitory effect on proximal tubular sodium reabsorption prestimulated by ANG II infusion.     

Effect of catecholamines and insulin on plasma volume and intravascular mass of albumin in man

1. The effect of intravenous catecholamine infusions and of intravenous insulin on plasma volume and intravascular mass of albumin was investigated in healthy males. 2. Physiological doses of adrenaline (0.5 microgram/min and 3 microgram/min) increased peripheral venous packed cell volume significantly; intravenous noradrenaline at 0.5 microgram/min had no effect on packed cell volume, whereas packed cell volume increased significantly at 3 micrograms of noradrenaline/min. No significant change in packed cell volume was found during saline infusion. 3. During adrenaline infusion at 6 micrograms/min, packed cell volume increased, plasma volume decreased and intravascular mass of albumin decreased significantly. During noradrenaline infusion at 6 micrograms/min, packed cell volume increased and plasma volume decreased, but intravascular mass of albumin did not change. 4. Application of a hyperinsulinaemic, euglycaemic glucose clamp led to an increase in transcapillary escape rate of albumin and a decrease in intravascular mass of albumin. Packed cell volume remained constant, while plasma volume, measured by radiolabelled albumin, decreased. 5. We conclude that the previously reported changes in packed cell volume, plasma volume, intravascular mass of albumin and transcapillary escape rate of albumin during hypoglycaemia may be explained by the combined actions of adrenaline and insulin.     

Effects of acute hypermagnesaemia on intracellular calcium concentration and adrenergic activity

The effects of acute hypermagnesaemia on intracellular free calcium and adrenergic activity were investigated in six normotensive volunteers given intravenous magnesium sulphate for 3 h. The free calcium concentration in platelets decreased after the first hour of infusion (P less than 0.05), but did not remain significantly depressed after 2 and 3 h of continued infusion. Plasma noradrenaline increased during the infusion (P less than 0.05), with no change in plasma adrenaline. The results demonstrate that the effects of intravenous magnesium sulphate on free intracellular calcium and plasma catecholamines are similar to those described with calcium antagonists.     

Arterial blood-pressure change and endogenous circulating substance P in man

Summary. Substance P (SP) is a powerful vasodilator and this peptide is today considered to be a chemical messenger. The potential effects on circulating SP of acute changes in arterial blood-pressure were investigated in nine subjects. An increase in arterial mean blood-pressure (+33%, P<0–001, n=9) was obtained by infusion of angiotensin II and a decrease in pressure (-10%, P, <0–005, n=6) was obtained by ganglionic blockade. The concentration of SP in plasma, from supine subjects in the normotensive condition, ranged from 3 to 13 pmol/1 (with a mean of 5–6 pmol/1). SP was thus within the reference interval: 3–16 pmol/1 (n.s.). Plasma SP remained very constant in each subject during the changes in blood-pressure (mean variation in plasma concentration of SP was 0–97 (SD) pmol/1). The results show that acute changes in arterial blood-pressure do not result in any detectable change in plasma SP, this seems to indicate that endogenous circulating SP has no significant role in the vascular tonus controlled by the arterial baroreflex.     

Effect of ganglionic blockade on endogenous circulating pancreatic polypeptide, vasoactive intestinal polypeptide, substance P, neurotensin and noradrenaline in healthy controls and long-term insulin-dependent diabetic patients

Plasma pancreatic polypeptide (PP), vasoactive intestinal polypeptide (VIP), substance P (SP), neurotensin (NT) and noradrenaline (NA) were measured in eight healthy subjects and 12 long-term insulin-dependent diabetic patients with and without autonomic neuropathy, before and after intravenous infusion of the ganglionic blocking agent trimethaphan camsylate, in order to determine the influence of the autonomic nervous system on the baseline values of the substances. The basal levels of the measured substances were not significantly different in healthy subjects and patients with or without diabetic autonomic neuropathy. In healthy subjects, the ganglionic blockade induced a significant decrease in PP (80%) (P less than 0.02), NA (58%) (P less than 0.05), NT (27%) (P less than 0.05) and a significant increase in SP (30%) (P less than 0.05), while the VIP concentration remained unchanged. The diabetic patients had nearly the same significant decrease in PP (68%) (P less than 0.01), NA (50%) (P less than 0.01), NT (22%) (P less than 0.02), VIP (21%) (P less than 0.05) and increase in SP (73%) (P less than 0.01). No relationship was found between the autonomic neuropathy and changes of the substances during ganglionic blockade. The results indicate that the postganglionic part of the autonomic nervous system participates in the maintenance of a normal baseline level of PP, NT and NA, but not of VIP. The regulation of VIP may be disturbed in long-term diabetic subjects.     

Effect of eprosartan on catecholamines and peripheral haemodynamics in subjects with insulin-induced hypoglycaemia

ANG II (angiotensin II) facilitates catecholamine release from the adrenal medulla and neuronal NE (noradrenaline) release. Since animal experiments point to specific sympatho-inhibitory properties of the AT1 (ANG II type 1)-receptor blocker EPRO (eprosartan), the primary aim of this study was to clarify if EPRO inhibits sympathetic reactivity in humans as determined by the effect of EPRO on insulin-induced catecholamine release. Sixteen healthy male volunteers were randomized in a double-blind cross-over study to receive a single dose of EPRO (600 mg) compared with placebo, followed by insulin-induced hypoglycaemia [0.15 IU (international unit)/kg of body weight; intravenous bolus] on two study days 1 week apart. From baseline to the end of hypoglycaemia (170 min), the sympatho-adrenal reactivity was mapped by invasive continuous blood pressure monitoring and repeated measurements of FBF (forearm blood flow), arterial and venous concentrations of glucose, catecholamines [EPI (adrenaline) and NE (noradrenaline)], renin, ANG II and aldosterone. EPRO induced an 8-10-fold increase in plasma renin and ANG II concentrations compared with placebo. Plasma glucose decreased equally during placebo and EPRO from baseline 5.9 mmol/l to 1.9 mmol/l and 2.1 mmol/l respectively, inducing a 17-fold increase in arterial EPI concentration at peak. The AUC (area under the curve) during hypoglycaemia for arterial EPI concentrations was 314+/-48 nmol.min.l-1 in placebo compared with 254+/-26 nmol.min.l-1 following EPRO treatment (P=0.14). EPRO attenuated the corresponding AUC for the EPI-induced pulse pressure response (4670+/-219 mmHg.min in EPRO compared with 5004+/-266 mmHg.min in placebo; P=0.02). Moreover, EPRO caused a less pronounced increase in FBF compared with placebo (402+/-30 compared with 479+/-46 ml.100 g-1 of body weight; P=0.04). Musculocutaneous NE release was not affected by EPRO and the AUC for NE release was 51.69+/-15.5 pmol.min-1.100 g-1 of body weight in placebo compared with 39.35+/-18.2 pmol.min-1.100 g-1 of body weight after EPRO treatment (P=0.57). In conclusion, EPRO did not significantly inhibit sympathetic reactivity compared with placebo; however, it blunted the haemodynamic responses elicited by the sympatho-adrenal stimulation which only tended to be attenuated by this drug.     

Cardiac and whole-body [3H]noradrenaline kinetics during adrenaline infusion in man.

1. To investigate the possible role of adrenaline as a modulator of noradrenaline release from the sympathetic nervous system, the responses of cardiac and whole-body noradrenaline kinetics to intravenous infusions of adrenaline (30 ng min-1 kg-1) and matching saline placebo were determined at rest and during supine bicycle exercise in 16 patients undergoing cardiac catheterization, in whom beta-adrenoceptor antagonists had been discontinued for 72 h. 2. At rest and compared with placebo, infusion of adrenaline was associated with a small increase in arterial plasma noradrenaline from 211 +/- 29 pg/ml to 245 +/- 29 pg/ml (P less than 0.05). Increases in whole-body noradrenaline spillover to arterial plasma were larger (from 282 +/- 40 ng min-1 m-2 to 358 +/- 41 ng min-1 m-2, P less than 0.01) and there was a trend towards an increase in whole-body noradrenaline clearance. Cardiac noradrenaline clearance was modestly increased during adrenaline infusion, but cardiac noradrenaline spillover was not altered despite increases in heart rate and coronary sinus plasma flow. Adrenaline infusion was associated with symptomatic myocardial ischaemia in four of 14 patients with coronary heart disease. 3. Supine bicycle exercise was associated with significant increases in peripheral noradrenaline concentrations and in cardiac and whole-body noradrenaline spillover. The increases on exercise were not significantly different for these variables during saline and adrenaline infusions. 4. Infusion of adrenaline to produce 'physiological' increases in plasma adrenaline concentration was associated with an increase in total noradrenaline release, as assessed by whole-body noradrenaline spillover to plasma.(ABSTRACT TRUNCATED AT 250 WORDS)     

EFFECTS OF KETANSERIN ON CARDIOVASCULAR, SYMPATHO-ADRENAL AND ENDOCRINE SYSTEMS DURING PHYSICAL EXERCISE IN MAN

Blood pressure, heart rate, oxygen consumption, plasma concentrations of catecholamines, renin, aldosterone and lactate were measured in 6 normotensive volunteers during a randomized cross-over study of oral ketanserin (20 mg X 7) and placebo; measurements were made at rest and during maximal dynamic exercise on a bicycle ergometer. At rest ketanserin reduced blood pressure without modifying heart rate or plasma noradrenaline and adrenaline. Duration of exercise and blood lactate levels did not differ between the ketanserin and the control group. During exercise only systolic blood pressure was significantly decreased on ketanserin at maximal work rate whereas heart rate did not change. Plasma noradrenaline was significantly increased and plasma aldosterone significantly decreased during exercise in ketanserin-treated subjects whereas plasma renin activity and plasma adrenaline remained unchanged. Finally, under ketanserin oxygen consumption during exercise was reduced. The results suggest that ketanserin might interfere with the sympathetic nervous system and aldosterone secretion in man.     

Compartmentalization of angiotensin II generation in the dog heart. Evidence for independent mechanisms in intravascular and interstitial spaces.

Angiotensin-converting enzyme inhibitors have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. In this study, we measure for the first time ANG I and ANG II levels in the interstitial fluid (ISF) space of the heart. ISF and aortic plasma ANG I and II levels were obtained at baseline, during intravenous infusion of ANG I (5 microM, 0.1 ml/min, 60 min), and during ANG I + the angiotensin-converting enzyme inhibitor captopril (cap) (2.5 mM, 0.1 ml/min, 60 min) in six anesthetized open-chested dogs. ISF samples were obtained using microdialysis probes inserted into the left ventricular myocardium (3-4 probes/dog). ANG I increased mean arterial pressure from 102+/-3 (SEM) to 124+/-3 mmHg (P < 0.01); addition of cap decreased MAP to 95+/-3 mmHg (P < 0.01). ANG I infusion increased aortic plasma ANG I and ANG II (pg/ml) (ANG I = 101+/-129 to 370+/-158 pg/ml, P < 0.01; and ANG II = 22+/-40 to 466+/-49, P < 0.01); addition of cap further increased ANG I (1,790+/-158, P < 0.01) and decreased ANG II (33+/-49, P < 0.01). ISF ANG I and ANG II levels (pg/ml) were > 100-fold higher than plasma levels, and did not change from baseline (8,122+/-528 and 6,333+/-677), during ANG I (8,269+/-502 and 6, 139+/-695) or ANG I + cap (8,753+/-502 and 5,884+/-695). The finding of very high ANG I and ANG II levels in the ISF vs. intravascular space that are not affected by IV ANG I or cap suggests that ANG II production and/or degradation in the heart is compartmentalized and mediated by different enzymatic mechanisms in the interstitial and intravascular spaces.     

Alpha-adrenoceptor blockade by phentolamine inhibits adrenaline-induced platelet activation in vivo without affecting resting measurements.

1. The effects of phentolamine (500 micrograms/min) on platelet aggregability in vivo at rest and during adrenaline infusion were assessed by ex vivo filtragometry and measurements of plasma beta-thromboglobulin levels in 10 healthy male subjects. Plasma levels of von Willebrand factor antigen and free fatty acids were also measured. 2. Adrenaline induced marked and expected increases in heart rate and systolic blood pressure and decreased diastolic blood pressure when venous plasma adrenaline levels were elevated from 0.12 +/- 0.02 to 2.9 +/- 0.3 nmol/l (P less than 0.01). 3. Adrenaline caused platelet activation in vivo. Ex vivo filtragometry readings were shortened by 58 +/- 9% (P less than 0.01), plasma beta-thromboglobulin levels increased by 99 +/- 44% (P less than 0.01) and platelet counts increased by 26 +/- 6% (P less than 0.01). Plasma levels of von Willebrand factor antigen and free fatty acids increased by 53 +/- 5% and 475 +/- 113% (both P less than 0.01), respectively. 4. Phentolamine enhanced the beta-adrenergic vasodilator responses to adrenaline, as both the decrease in diastolic blood pressure and the reflexogenic increase in heart rate were enhanced (both P less than 0.01). Marked elevations in plasma noradrenaline levels were found during infusions of phentolamine and adrenaline (P less than 0.001). 5. Phentolamine did not alter platelet indices at rest, but abolished adrenaline-induced platelet activation, as filtragometry readings, plasma beta-thromboglobulin levels and platelet counts remained at, or below, resting levels. Responses of plasma levels of von Willebrand factor antigen and free fatty acids to adrenaline were not influenced by phentolamine and did not seem to influence platelet responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulating adrenaline and blood pressure: the metabolic effects and kinetics of infused adrenaline in man

Abstract. Six normotensive volunteers were infused with L-adrenaline at 001, 003, 005, 0075 and 010 μg/kg^-1 min^-1, each increment lasted 10 min. Plasma adrenaline rose from 0–27 to 4–61 nmol/1, and there were dose-related increases in plasma renin activity, blood glucose, plasma cyclic AMP and plasma free fatty acids, but not in plasma noradrenaline and cyclic GMP. Levels of circulating adrenaline previously noted in essential hypertensives had minimal cardiovascular effects. The secretion rate of adrenaline and its rate of clearance from the circulation were calculated from plasma samples taken during an hour-long infusion (0–083 ± 0006 μg kg^-1 min^-1) of L-adrenaline in the same individuals. The secretion rate ranged from 1 40 to 601 nmol/min with a mean (±SEM, 6) of 2–82 ±0–76 nmol/min. Mean clearance (±SEM, 6) was 9–41 ± 1 -37 1/min and ranged from 4–86 to 14.611/min. The decline of plasma adrenaline following the infusion was biexponential.
Plasma adrenaline is unlikely to be of primary importance in the elevation of blood pressure, either directly, via renin release or by noradrenaline release via presynaptic beta receptors. However, variation in clearance between subjects limits the use of plasma levels as an interindividual index of adrenal release of adrenaline. The relationship between sympathoadrenal activity and plasma adrenaline may be further perturbed by equilibration between the circulation and sites of tissue uptake. The lower levels of plasma adrenaline than of noradrenaline appear to result from both a slower rate of secretion and a higher rate of clearance from the circulation.     

The effect of prostaglandin E1 upon the pressor and hormonal response to exogenous angiotensin II in human pregnancy

The effect of prostaglandin E1 (PGE1) on the pressor and hormonal response to angiotensin (ANG) II has been studied in 22 women in second trimester pregnancy. Three-point dose-response curves were initially determined for all women. Eleven then received an infusion of PGE1 while the remainder received an infusion of normal saline as controls. The dose-response curves to ANG II were re-studied after a period of stabilization. Although assignation to treatment group was random, differences were found in age and basal blood pressure between the control group and those given PGE1. The pressor data from the PGE1 group were thus split by age for analysis. The administration of ANG II alone was associated with significant (P less than 0.001 at all doses) pressor effects without accompanying bradycardia. Plasma renin concentration (PRC) was suppressed (P less than 0.001). Plasma aldosterone concentration rose (P less than 0.001), the magnitude of the rise being directly associated with the plasma ANG II concentrations achieved (P less than 0.05). The infusion of PGE1 had no significant effect on basal blood pressure, but evoked a sustained tachycardia in both age groups (P less than 0.001). Basal hormone concentrations were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of oxygen withdrawal on catecholamine release in patients on home oxygen therapy

1. Long-term oxygen therapy in appropriate patients prolongs survival and corrects neuropsychological function. Some tests of mental function paradoxically improve during short periods of oxygen withdrawal in patients on long-term oxygen therapy, although the mechanism of this response is unknown. 2. To evaluate the effects of transient hypoxaemia on plasma adrenaline and noradrenaline levels, we studied eight oxygen-dependent patients who underwent either a 4 h period of oxygen withdrawal or their routine therapy, in a randomized, blinded fashion, on 2 separate days. 3. Plasma noradrenaline did not differ at baseline between study days. During normoxic conditions, plasma noradrenaline levels did not increase significantly with time. By contrast, under hypoxic conditions, plasma levels of noradrenaline rose significantly from 0 to 4 h (P less than 0.05). The magnitude of the noradrenaline response was correlated with baseline noradrenaline such that subjects with the highest resting levels had the largest increase during hypoxia (r = 0.95, P less than 0.001). 4. Plasma adrenaline did not differ at baseline between study days and there were no significant effects of hypoxia on plasma adrenaline levels. 5. We conclude that the sympathetic nervous system, but not the adrenal medulla, is stimulated in chronically oxygen-dependent subjects made acutely hypoxaemic. The magnitude of this stimulation appears to be related to the state of sympathetic nervous system activity at baseline. Improvement in some tests of mental function during transient periods of oxygen withdrawal may be due to non-specific arousal caused by a catecholamine surge.     

Neuronal re-uptake of noradrenaline by sympathetic nerves in humans.

1. Plasma concentrations of [3H]dihydroxyphenylglycol, the intraneuronal metabolite of noradrenaline, were examined during intravenous infusion of [3H]noradrenaline in 43 subjects, to assess the nature of its formation. Noradrenaline re-uptake by sympathetic nerves was estimated in 11 subjects from the effects of neuronal uptake blockade with desipramine on noradrenaline clearance and plasma concentrations of [3H]dihydroxyphenylglycol and endogenous dihydroxyphenylglycol. In seven subjects noradrenaline re-uptake and spillover into plasma were examined before and during mental arithmetic or handgrip exercise. 2. During infusion of [3H]noradrenaline, plasma [3H]dihydroxyphenylglycol increased progressively, indicating its formation from previously stored [3H]noradrenaline leaking from vesicles as well as from [3H]noradrenaline metabolism immediately after removal into sympathetic nerves. Thus, to estimate noradrenaline re-uptake, the amount of [3H]dihydroxyphenylglycol derived from [3H]noradrenaline metabolized immediately after removal into the sympathetic axoplasm must be isolated from that derived from [3H]noradrenaline sequestered into vesicles. 3. At rest in the supine position the rate of noradrenaline re-uptake was 474 +/- 122 pmol min-1 kg-1, 9.5-fold higher than the rate of spillover of noradrenaline into plasma (49.6 +/- 6.4 pmol min-1 kg-1). Noradrenaline re-uptake and spillover into plasma were both increased during mental arithmetic and isometric handgrip exercise.     

Plasma Catecholamines and Blood Substrate Concentrations: Studies in Insulin Induced Hypoglycaemia and after Adrenaline Infusions

Abstract. Plasma adrenaline-blood glucose interrelationships in insulin-induced hypoglycaemia in man have been studied using a sensitive double-isotope derivative method for adrenaline estimation. Plasma adrena-i-line reached a peak of 1. 24 ng/ml at 45 minutes after insulin while blood glucose reached a nadir of 22 mg/ 100 ml at 30 minutes. There was a strong correlation both between the rise in adrenaline and the degree of hypoglycaemia and between the rise in adrenaline and the post-hypoglycaemic rise in glucose. Plasma noradrenaline rose from 0. 29 to 0. 59 ng/ml, the rise correlating with the rise in adrenaline. Changes in pulse rate preceded and were unrelated to changes in plasma catecholamines. Fuel mobilisation in response to adrenaline infusion (6 μg/min. for 20 min.) in normoglycaemic man was also studied. Plasma adrenaline concentration rose from a mean of 0. 02 ng/ml to 0. 71 ng/ml while plasma noradrenaline concentration was unchanged. Blood glucose rose from 71 to 98 mg/100 ml while plasma insulin decreased from 11 to 8 yU/ml. Blood lactate rose by 0. 85 mM while pyruvate concentration remained unchanged. Blood glycerol concentration rose twofold and ketone body concentration threefold but there was little change in the concentrations of the glucogenic amino acids, alanine, glutamate and glutamine. Both the 3-hydroxybutyrate/acetoacetate ratio and the lactate/pyruvate ratio rose implying a more reduced intracellular state due presumably to increased hepatic fatty acid oxidation. It is concluded that adrenaline enhances the recycling of lactate and spares glucose through the mobilitsation of lipids but that amino acids are little affected.     

Cardiovascular and adrenergic effects of cigarette smoking during immediate non-selective and selective beta adrenoceptor blockade in humans

The cardiovascular and adrenergic responses to cigarette smoking during acute selective and non-selective beta adrenoceptor blockade were studied in seven young healthy volunteers in a double blind cross-over fashion. Heart rate, arterial blood pressure, forearm blood flow and plasma levels of adrenaline and noradrenaline were determined before and during the terminal 5 min period of 15 min smoking test. During smoking, plasma concentrations of adrenaline increased markedly and evenly by approximately 0.3 ng/ml in all three experimental sessions. Plasma concentrations of noradrenaline remained unchanged. Propranolol, a non-selective beta blocker, caused a marked rise in diastolic and mean blood pressure and forearm vascular resistance during smoking. This response was not seen in the control series or after selective beta-1 blockage with atenolol. This difference is attributable to propranolol's blockade of adrenaline's vasodilating effect mediated by beta-2 receptors in the resistance vessels. Furthermore, atenolol attenuated the systolic blood pressure and tachycardiac responses induced by cigarette smoking by comparison with placebo. This study suggests that selective beta-1 blockers are preferable in the management of patients who are habitual smokers.     

Responses of the systemic circulation and of the renin-angiotensin-aldosterone system to ketanserin at rest and exercise in normal man

The systemic circulation at rest and during exercise was studied in ten normal male volunteers, after placebo on one occasion and after acute intravenous administration of the serotonergic antagonist ketanserin on another occasion. The effects of ketanserin on the components of the renin-angiotensin-aldosterone system, on plasma catecholamines and on exercise capacity for graded uninterrupted exercise were also investigated. At rest in recumbency rapid intravenous injection of 10 mg of ketanserin, followed by a continuous infusion of 2 mg/h, produced an acute but transient fall in mean intra-arterial pressure of 6 mmHg compared with placebo. After 15 min the mean arterial pressure with ketanserin was within 2 mmHg of the mean pressure with placebo. In the sitting position both at rest and up to 30% of maximal work rate, the mean arterial pressure during ketanserin did not differ from the pressure on placebo. However, at higher levels of physical activity the rise in mean arterial pressure was lower with ketanserin; the pressure achieved with placebo was 7.5 mmHg higher at maximal work rate. Heart rate and cardiac output were significantly higher during ketanserin. When the subjects were lying down and resting, plasma noradrenaline and adrenaline levels, plasma renin activity and angiotensin II concentration were not affected by ketanserin; however, these values were higher in the sitting position both at rest and during exercise. Plasma aldosterone was reduced by ketanserin during exercise and also when the subject was resting in the recumbent position.(ABSTRACT TRUNCATED AT 250 WORDS)