CHANGES IN PLASMA NORADRENALINE AND ADRENALINE DURING ISOMETRIC EXERCISE

1. Plasma noradrenaline and adrenaline were measured radioenzymatically in twelve hypertensive and four normotensive subjects before and during handgrip. In the resting arm (n= 11), plasma noradrenaline increased by 17% (P<0 01) and plasma adrenaline by 27% (P<0 01). In the exercising arm, plasma adrenaline increased by 97% (P< 0 005) but the mean increase of noradrenaline of 10% was not significant (P>0 1). 2. The noradrenaline response suggests a small and variable sympathetic adrenergic response; the significant difference (P<0 05) in adrenaline responses between resting and exercising arms may reflect local variation in tissue clearance.     

INCREASED PLASMA NORADRENALINE DURING LOW DOSE ADRENALINE INFUSION IN RESTING MAN AND DURING SYMPATHETIC STIMULATION

Both resting and stimulated (straight-leg raising and head-up tilt) levels of arterial and venous plasma noradrenaline were significantly higher during low-dose adrenaline infusion in five mild hypertensive and four normotensive patients with one adrenal. Repeat adrenaline infusions in the five hypertensive patients while measuring noradrenaline clearance (3H-noradrenaline constant infusion) achieved similar levels of plasma adrenaline, and similar increases in plasma noradrenaline, within five min of achieving target infusion rate. Increased plasma noradrenaline was not explained by reduced clearance. These results are consistent with the hypothesis that physiological concentrations of adrenaline are capable of facilitating noradrenaline release in man.     

FREE AND CONJUGATED CATECHOLAMINES IN HUMAN PLASMA DURING PHYSICAL EXERCISE

To investigate changes of free and sulfoconjugated catecholamines in response to alterations in sympatho-adrenal activity, free and conjugated noradrenaline, adrenaline and dopamine were determined radioenzymatically in plasma of 49 subjects. During brief vigorous bicycle exercise (8 min, maximal heart rate: 177 beats/min) mean free noradrenaline and adrenaline values of 2.0 and 0.51 nmol/l at rest, increased to 6.7 and 2 nmol/l (P less than 0.001) respectively, at the maximal workload of 200 watt, whereas conjugated noradrenaline and adrenaline decreased from 3.4 and 0.8 nmol/l to 2.1 and 0.4 nmol/l (P less than 0.001) respectively. In the tenth min of the recovery period basal free and conjugated noradrenaline and adrenaline levels were measured. The moderate stress of a steam bath (20 min, maximal heart rate: 131 beats/min) doubled free noradrenaline and adrenaline levels. However, conjugated noradrenaline and adrenaline concentrations remained unchanged. The increase in free catecholamine values during an exhausting cross-country march over 20 km was associated with an accumulation of sulfated catecholamines. After a rest of 30 min free noradrenaline and adrenaline reached basal values, whereas conjugated noradrenaline and adrenaline remained elevated by 64 and 70% respectively, compared to pre-exercise concentrations. It was concluded that conjugated noradrenaline and adrenaline may be used as pools for free noradrenaline and adrenaline during brief vigorous exercise. In addition, they may also be indicators of chronic activation of the sympatho-adrenal system.     

EFFECT OF PREGNANCY IN THE RABBIT ON THE PRESSOR RESPONSE TO ANGIOTENSIN AND NORADRENALINE

The pressor responses to angiotensin II injections of 29, 117 and 468 pmol/kg and infusion at 54 pmol/kg per min were compared in near-term pregnant and matched non-pregnant rabbits. The responses to noradrenaline injections of 652, 2608 and 10 432 pmol/kg and infusion at 1185 pmol/kg per min were similarly compared. At all doses of angiotensin and noradrenaline, whether by injection or infusion, the response of the pregnant animals was significantly greater. However the control arterial pressures of the pregnant rabbits were lower and fell in a range where the baroreceptor reflex might be less effective. Thus less efficient buffering could contribute to the greater response to the vasoconstrictor agents. To test the effect of pregnancy on the vascular response to angiotensin and noradrenaline when reflex and central effects were excluded, hexamethonium was used to produce autonomic ganglion blockade. The response to both vasoconstrictors was now less in the pregnant rabbits than in the non-pregnant. Thus in assessing the effects of pregnancy on the responses of the rabbit to angiotensin and noradrenaline the effect of pregnancy on mean blood pressure must be taken into account, since this can influence the extent to which the arterial baroreceptors may modulate the response.     

DISSOCIATION OF BLOOD PRESSURE AND ALBUMINURIA IN NORMAL SUBJECTS INFUSED WITH ANGIOTENSIN II AND NORADRENALINE

1. Albuminuria is a predictor of diabetic renal disease and atherosclerosis. Changes in blood pressure (BP) may influence albuminuria. 2. The effect of acute BP elevation on albumin excretion rates (AER) using noradrenaline (NA) and angiotensin II (AII) infusions in six normal subjects was examined. 3. The average rise in BP during a 120 min infusion was 23 mmHg for AII and 16 mmHg for NA. 4. There was a marked dissociation between AER and BP levels in both AII and NA infusions. 5. Previously described correlations between BP and AER in ambulatory BP studies may be explained by other factors such as exercise and postural changes.     

ENALAPRIL DECREASES PLASMA NORADRENALINE LEVELS DURING THE COLD PRESSOR TEST IN HUMAN HYPERTENSIVES

1. The effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on the responses of blood pressure and plasma catecholamine levels to the cold pressor test in human hypertensives were examined. 2. Systolic and diastolic blood pressure decreased significantly after treatment with enalapril (5 mg/day for 4 weeks) as did the resting level of plasma noradrenaline. 3. The cold pressor test induced a rise in blood pressure and plasma noradrenaline levels. After 2 and 4 weeks enalapril treatment, the rises in the plasma noradrenaline level and systolic and diastolic pressure due to cold pressor test were reduced significantly. 4. These results suggest that ACE inhibition has a sympatho-inhibitory effect. One possible explanation is that enalapril reduces angiotensin II formation thus decreasing the activation of release-enhancing angiotensin II receptors on postganglionic sympathetic nerve endings.     

ENDOTHELIN-1 ENHANCES VASOCONSTRICTOR RESPONSES TO SYMPATHETIC NERVE STIMULATION AND NORADRENALINE IN THE RABBIT EAR ARTERY

1. In rabbit isolated perfused ear arteries denuded of endothelium, a low concentration of endothelin-1 (0.1 nmol/L) that had no direct vasoconstrictor action produced slowly developing enhancements of vasoconstrictor responses to noradrenaline and sympathetic nerve stimulation. The enhancements reached maximal levels after 60 min of exposure to endothelin-1. 2. A higher concentration of endothelin-1 (1 nmol/L), which produced a slow-developing increase in perfusion pressure of 70 mmHg over the course of 1 h, significantly enhanced vasoconstrictor responses to sympathetic nerve stimulation for the first 30 min, after which there was no significant enhancement. Responses to noradrenaline were not enhanced by 1 nmol/L endothelin-1. 3. The enhancing effect of low concentrations of endothelin-1 on vasoconstrictor responses to sympathetic nerve stimulation and noradrenaline may play a physiological role in modulating vasomotor function.     

EFFECTS OF RESERPINE ON THE CONTENT AND UPTAKE OF DOPAMINE AND NORADRENALINE IN RABBIT ARTERIES

1. Change with time of the content and uptake of dopamine (DA) and noradrenaline (NA) in the renal, superior mesenteric and femoral arteries and abdominal aorta of rabbit after reserpine administration was examined. Endogenous DA and NA were measured by high performance liquid chromatography coupled with electrochemical detector. 2. A single dose of reserpine (3 mg/kg, i.p.) maximally depleted the endogenous DA and NA contents in the four blood vessels 24 h after the administration; the ratios of reductions were 70–90% and approximately 90% of the normal levels, respectively. The DA contents in all four vessels recovered to the normal level within 4 days after reserpine. However, NA content did not recover to the normal levels within 30 days after reserpine except in the mesenteric artery. 3. The activity of dopamine β-hydroxylase (DBH) significantly increased in all four blood vessels 1 h after reserpine. Although the DBH activity returned to the normal level after 3 days in the mesenteric artery, it returned within 24 h in the other three vessels. 4. [³H]-Dopamine and [³H]-NA uptake were almost completely depressed 1 h after reserpine. The [³H]-NA uptake in four vessels recovered to the normal level 2–14 days after reserpine, and [³H]-DA uptake recovered after 30–45 days. Thus, the endogenous DA content in blood vessels was completely restored although DA uptake and NA content were still affected. 5. These results suggested that the recovery of stored DA after reserpine was faster than that of stored NA and the recovery of DA uptake after reserpine was slower than NA uptake. This indicates a possibility that a part of DA pool may be different from NA pool in adrenergic nerve terminals in the blood vessels.     

WHOLE BODY AND RENAL NORADRENALINE RELEASE DURING ACUTE INFUSION OF ENDOTHELIN-1 IN CONSCIOUS SHEEP

1. The present study investigated in conscious sheep the response of the sympathetic nervous system to a systemic infusion of 20 nmol/h endothelin-1 (ET-l), using a tritiated-noradrenaline (NA) tracer dilution technique. 2. Mean arterial pressure increased from 79 ±3 mmHg to a maximal level of 102± 12 mmHg by 30 min of ET-1 infusion. 3. Total and renal NA kinetics were measured during this time. Total NA spillover was not affected by infusion of ET-1. In contrast, renal NA spillover decreased from a control level of 81 ± 5 to 30 ± 14ng/min (P<0.01) after 20 min and to 27 ± 7ng/min (P<0.01) after 30 min of ET-1 infusion. 4. The present findings are consistent with the proposal that a direct vasoconstrictor action of ET-1 results in a paroreflex mediated reduction in renal sympathetic vasoconstrictor activity.     

RESPONSE OF ATRIAL NATRIURETIC PEPTIDE TO ADRENALINE AND NORADRENALINE INFUSION IN MAN

1. Atrial natriuretic peptide (ANP) levels were significantly increased during both adrenaline and noradrenaline infusions, in the physiological range, in normal subjects and in patients with essential hypertension. 2. During adrenaline infusion significant increases in both circulating adrenaline and noradrenaline levels were observed. Mean arterial pressure was unaltered. Changes in heart rate were not significant. 3. During noradrenaline infusion, significant increases in circulating noradrenaline and mean arterial pressure were also observed. Heart rate and plasma adrenaline levels were unaltered. 4. Fluctuations in sympathetic nervous system activity may be involved in the regulation of ANP via adrenoceptor stimulated release of ANP. Other known regulators such as atrial stretch and increasing heart rate may modify this response.     

NORADRENALINE RELEASE FROM THE RAT HEART DURING ANOXIA: EFFECTS OF CHANGES IN EXTRACELLULAR SODIUM CONCENTRATION AND INHIBITION OF SODIUM UPTAKE MECHANISMS

1. Anoxic perfusion of the isolated rat heart releases noradrenaline in the absence of sympathetic nerve fibre stimulation. 2. Anoxic noradrenaline release is enhanced by reducing the extracellular Na+ concentration, consistent with the proposal that such release occurs by carrier-mediated efflux. 3. Release is also enhanced by lignocaine but inhibited by amiloride and ethylisopropylamiloride, suggesting that sodium entry into adrenergic nerve terminals during anoxia occurs by Na+/H+ (and possibly Na+/Ca2+) exchange.     

A COMPARISON OF THE CARDIAC ACTIONS OF DOPAMINE AND NORADRENALINE IN ANAESTHETIZED DOGS AND GUINEA-PIG ATRIA

1. The positive chronotropic and inotropic actions of dopamine and noradrena-line have been compared in anaesthetized dogs and isolated guinea-pig atria. 2. Inotropic activity was measured with a strain-gauge arch in vagotomized dogs or estimated from max (dp/dt) in dogs with denervated hearts. 3. The effects of propranolol and haloperidol on the concentration-response curves to both amines were studied in isolated atria. 4. In anaesthetized vagotomized dogs noradrenaline was more potent than dopamine but dopamine appeared to have a selective inotropic action, less apparent with noradrenaline. In denervated hearts, doses of noradrenaline and dopamine which caused similar increases in max (dp/dt) also caused similar increases in heart rate. 5. In isolated atrial preparations, concentrations of dopamine and noradrenaline which produced similar increases in force of contraction also had similar chronotropic effects. 6. Propranolol produced a shift to the right of the concentration-response curves to both dopamine and noradrenaline but the antagonism of noradrenaline was quantitatively greater. Haloperidol had no effect in concentrations below those found to cause general tissue depression. 7. It is concluded that neither dopamine nor noradrenaline show any real difference in their relative inotropic and chronotropic activities in the absence of autonomic innervation.     

INHIBITION BY HYDRALAZINE OF THE CONVERSION OF DOPAMINE TO NORADRENALINE IN RAT ATRIA IN VITRO AND IN VIVO

1. Hydralazine (10 to 2000 μnol/1) produced a concentration-dependent inhibition of the conversion of (³H)-dopamine to (³H)-noradrenaline in rat isolated atria. 2. In rats treated with hydralazine (2 mg/kg, i.p.), there was an inhibition of the conversion of (³H)-dopamine to (³H)-noradrenaline in the intact atria in vivo. 3. Hydralazine treatment may result in the appearance of dopamine as a significant co-transmitter in noradrenergic nerves, and this may contribute to the antihypertensive effect of hydralazine.     

DIFFERING NORADRENALINE KINETICS IN ESSENTIAL HYPERTENSION AND DEPRESSIVE ILLNESS, TWO DISEASES IN WHICH THE PLASMA CONCENTRATION OF NORADRENALINE IS SOMETIMES ELEVATED

1. The rate of spill-over of noradrenaline to plasma, and neuronal noradrenaline uptake, which influences spill-over, were studied in patients with essential hypertension and depressive illness. 2. Noradrenaline spill-over was increased in seven of thirty-four patients with essential hypertension and five of eleven patients with primary depressive illness, compared with values in seventeen normal subjects (range 1.0–3.63 nmol/min perm²). 3. Faulty neuronal reuptake of noradrenaline seemed to be the cause of higher noradrenaline spill-over in patients with essential hypertension. Increased sympathetic nerve firing rates apparently were responsible in the primary depres-sives, despite their normal blood pressure. 4. These puzzling findings suggest that hypertension occurs when neurotransmitter excess is due to defective noradrenaline reuptake (in essential hypertension), but not chronically increased nerve firing (in depressive illness).     

REGIONAL VARIATION IN THE RESPONSE OF THE RAT VAS DEFERENS TO FIELD STIMULATION, TO NORADRENALINE AND TO TYRAMINE

SUMMARY 1. Experiments were performed with preparations obtained by medial transection of the rat vas deferens providing urethral and testicular segments, to determine whether the smooth muscle of this organ responds uniformly along its length to field excitation of sympathetic nerve terminals and to sympathomimetic amines. 2. Both preparations responded to pulses applied at 0.1 Hz with twitches which were blocked by guanethidine (1–10 μM) indicating that sympathetic nerve terminals were being stimulated. Xylazine (0.01–1 μM) also blocked the twitches. 3. In response to stimulation at 0.1 Hz the twitches of the urethral segment were larger but briefer than those of the testicular segment. However, the increase in tension with increase in stimulation frequency over the range 0.01–10 Hz was greater in the testicular than in the urethral segment. After a train of pulses at 1 Hz or above, the first few twitches of the testicular segment evoked by pulses applied at 0.1 Hz were facilitated, whereas twitches of the urethral segment were inhibited. 4. Noradrenaline (1–100 μM) and tyramine (1–100 μM) regularly enhanced twitches in response to stimulation at 0.1 Hz in the testicular segment but often reduced those in the urethral segment. Contractions in response to these amines occurred more regularly and were stronger in the testicular than in the urethral segment. The α-adrenoreceptor antagonists phenoxybenzamine (0.01 μM), phentolamine (10 μM) and thymoxamine (10 μM) blocked contractions and blocked or reversed the twitch enhancement produced by noradrenaline and tyramine. These observations indicate that the density of excitatory α-adrenoreceptors is greater at the testicular end of the tissue. 6. Twitch inhibition evoked by noradrenaline or by tyramine in urethral segments was resistant to blockade by phenoxybenzamine (0.01 μM), phentolamine 10 μM), thymoxamine (10μM) and propranolol (10 μM). 7. A histological comparison of the two ends of the vas deferens indicated that at the urethral end there was more circularly arranged muscle and that this interrupted bundles of longitudinally arranged muscle. The testicular end was thinner but had the higher proportion of longitudinally arranged fibres. 8. The differences between the two ends of the vas deferens in the arrangement of muscle layers and in the response to sympathetic nerve stimulation and to drugs may be of physiological significance in relation to the transport of sperm from the epididymis to the urethra.     

EFFECTS OF RESERPINE TREATMENT ON ARRHYTHMOGENESIS DURING ISCHAEMIA AND REPERFUSION IN THE ISOLATED RAT HEART

1. The effects of reserpine treatment on the myocardial contents of catecholamines and enkephalins and the incidence of ventricular arrhythmias during ischaemia and reperfusion in the isolated rat heart were studied. 2. Reserpine treatment almost completely depleted the heart of noradrenaline (NA). It also significantly depleted the heart of adrenaline and dopamines. It did not, however, alter the myocardial contents of enkephalins. 3. Reserpine-treatment attenuated significantly, but did not abolish, cardiac arrhythmias induced by ischaemia and reperfusion in the isolated heart preparation. 4. The results of the present study indicate that myocardial catecholamines especially NA are a contributing factor to arrhythmogenesis during ischaemia and reperfusion.     

PLASMA CATECHOLAMINE CONCENTRATIONS DURING MORPHINE WITHDRAWAL IN CONSCIOUS GUINEA-PIGS

1. Plasma noradrenaline (NA) and adrenaline (AD) concentrations and locomotor activity were measured in conscious normal and adrenalectomized guinea-pigs before and after injection of a single dose of morphine (15 mg/kg) and following precipitation of withdrawal with naloxone 2 h later. Arterial blood samples were obtained via carotid catheters inserted 3 days before experiment. Normal guinea-pigs given saline instead of morphine were used as controls. 2. Increased locomotor activity occurred following naloxone injection in both intact and adrenalectomized morphine-treated guinea-pigs. 3. Plasma AD concentration was significantly elevated only during the naloxone-precipitated withdrawal period, whereas plasma NA concentration was also elevated during the morphine treatment period. No significant changes occurred in saline-treated guinea-pigs given naloxone. 4. In adrenalectomized guinea-pigs AD did not reach detectable levels in the plasma at any time during the experiments, thus showing that the increased plasma AD level during morphine withdrawal in normal animals reflected adrenal medullary release. 5. It was concluded that measurements of plasma AD concentration and locomotor activity in guinea-pigs should be useful for the study of the interactions between behavioural and autonomic mechanisms involved in opiate dependence and withdrawal, since the effects of morphine and morphine withdrawal on the autonomic nervous system are clearly different in this species.     

母鸡在排卵周期和抱窝血浆“黄体生成素类似物”和孕酮的浓度变化

本文用放射免疫分析法(RTA)测定了泰和母鸡在排卵周期和抱窝的不同生殖阶段,血浆“黄体生成素类似物”(“LH”)和孕酮(P)的浓度。结果表明:母鸡在排卵周期血浆“LH”和P的平均值分别为3.67±0.60ng/ml(x±SE)和459.50±30.87pg/ml,排卵前6～3h,血浆“LH”和P均出现浓度高峰,其峰值比相应的平均值高出1.1和1.3倍,差异非常显著(P<0.01)。抱窝鸡血浆“LH”和P在24h内的平均值分别为2.27±0.22ng/ml和319.46±12.15pg/ml,显著地低于母鸡在排卵周期的平均值(P<0.05),且在24h内的不同时间,未见有浓度高峰出现。     

DIFFERENTIAL BLOCKING EFFECTS OF PRAZOSIN AND YOHIMBINE ON PRESSOR RESPONSES TO NEURONALLY RELEASED AND EXOGENOUSLY ADMINISTERED NORADRENALINE IN THE PITHED RAT

The effects of prazosin and yohimbine on pressor responses to sympathetic nerve stimulation and intravenous injections of noradrenaline, phenylephrine and clonidine were examined in pithed rats to determine the postjunctional location of alpha 2-adrenoceptors in the vascular smooth muscle. Prazosin antagonized the pressor responses to phenylephrine and to sympathetic nerve stimulation more effectively than the responses to noradrenaline and to clonidine. Yohimbine antagonized the pressor responses to noradrenaline and to clonidine more effectively than the responses to sympathetic nerve stimulation and to phenylephrine. These results suggest that alpha 2-adrenoceptors as well as alpha 1-adrenoceptors produce vasoconstriction in the rat vasculature and support the hypothesis that alpha 1-adrenoceptors are predominantly located within the neuroeffector junction in contrast to an extrajunctional location of alpha 2-adrenoceptors.