Effect of low dose adrenaline and noradrenaline infusions on airway calibre in asthmatic patients

Airway, cardiovascular and metabolic responses were measured in six asthmatic patients with stable asthma during separate adrenaline, noradrenaline and control infusions. Four incremental infusion rates (4, 10, 25 and 62.5 ng min-1 kg-1) produced circulating catecholamine concentrations within the physiological range. Specific airways conductance and maximal expiratory flow rates measured from complete and partial flow-volume curves increased significantly (P less than 0.05) during adrenaline infusion, in a dose-response manner. No changes in specific airways conductance or maximal expiratory flow rates were seen during the noradrenaline or control infusion. The highest adrenaline infusion rate caused a rise in systolic blood pressure (P less than 0.05) and plasma glucose (P less than 0.05) and a fall in plasma potassium (P less than 0.05). Noradrenaline infusion caused a slight increase in diastolic blood pressure (P less than 0.05) but no metabolic changes. No cardiovascular or metabolic changes occurred during the control infusion. Infused adrenaline, producing circulating concentrations within the physiological range, caused dose-related bronchodilatation in asthmatic patients. Circulating noradrenaline does not appear to have a role in the control of basal airway tone in asthmatic patients.     

Plasma volumes,noradrenaline levels and renin activity during posture changes in end-stage renal failure

Summary. In nine normal subjects and nine patients with end-stage chronic renal failure (CRF) we studied the effect of prolonged (110 min) postural changes on the plasma volume, intrathoracic volume, plasma noradrenaline concentration, haemodynamic variables, and plasma renin activity (PRA). Upon standing, plasma volume decreased rapidly by about 11% in both groups as measured from the control volume and changes in haematocrit. This was accompanied by identical increments of plasma colloid osmotic pressure. The changes in intrathoracic volume (monitored by measurement of the electrical impedance of the thorax), as well as the alterations in plasma noradrenaline, blood pressure, and heart rate, were also comparable in the two groups. These similarities were in contrast with divergent responses of PRA. The increase in PRA on standing was significantly blunted in the CRF patients compared with the normal response (to 1.4±0- 4 fold of the supine value in CRF v. 6.0±3.2 fold in the normals, P < 0.0004). It is concluded that the attenuated increase in PRA upon standing in patients with CRF is not a consequence of diminished sympathetic stimulation or an altered response of the intravascular volume. Second, the unabated decrease in plasma volume upon standing pleads against a decrease of tissue compliance in CRF.     

Changes in plasma catecholamines in response to reflex modulation of sympathetic vasoconstrictor tone by cardiopulmonary receptors

The effects of selective deactivation and stimulation of cardiopulmonary receptors on plasma noradrenaline (radioenzymatic method) were studied in nine normotensive subjects by reducing and increasing central venous pressure for 20 min via lower body suction and leg-raising manoeuvres that did not alter arterial blood pressure and heart rate. Deactivation of cardiopulmonary receptors was accompanied by a rise in plasma noradrenaline that achieved a peak within 5 min (91.8 +/- 22%, mean +/- SE) and was then sustained. Stimulation of cardiopulmonary receptors was accompanied by a fall in plasma noradrenaline (-16.6 +/- 3.4%) that levelled off at the second minute and was then sustained. On average the increase and the reduction in plasma noradrenaline had a time course and a magnitude similar to the increase (80.5 +/- 10.5%) and the reduction (-28.4 +/- 5%) in forearm vascular resistance (derived from plethysmographic flow measurement) concomitantly caused by cardiopulmonary receptors. Furthermore, analysis of individual data showed that changes in plasma noradrenaline and forearm vascular resistance were linked by a positive relationship (r = 0.64). Thus the cardiopulmonary receptor reflex can produce rapid, marked and sustained changes in both plasma noradrenaline and forearm vasomotor tone. This is in sharp contrast with the previously observed inability of the carotid baroreflex to alter both these humoral and haemodynamic variables. Taken together these findings support the hypothesis that sympathetic tone to skeletal muscle is an important determinant of the concentration of plasma noradrenaline in blood.     

Adrenoceptors mediating the cardiovascular and metabolic effects of alpha-methylnoradrenaline in humans

alpha-Methylnoradrenaline is a widely used tool to study alpha2-adrenoceptor function, but its selectivity for this receptor has not been validated in humans in vivo. To characterize the adrenoceptors mediating cardiovascular and metabolic effects of alpha-methylnoradrenaline in humans, we have performed graded i.v. infusions of alpha-methylnoradrenaline in a randomized, placebo-controlled crossover study in six young, healthy males in the absence and presence of the beta-adrenoceptor antagonist propranolol, the alpha1-adrenoceptor antagonist doxazosin, and the alpha2-adrenoceptor antagonist yohimbine. alpha-Methylnoradrenaline dose-dependently increased heart rate, systolic blood pressure, cardiac output, blood glucose, serum insulin, free fatty acids, and gastrin, shortened the duration of heart rate-corrected electromechanical systole, and decreased diastolic blood pressure, total peripheral resistance, and plasma noradrenaline. Propranolol completely reversed the rise in heart rate and cardiac output, the fall in peripheral resistance, the shortening of electromechanical systole, and the rise in insulin; it blunted the increase in free fatty acids and gastrin. Yohimbine did not significantly influence most parameters but significantly potentiated the rise in insulin, blunted the increase in glucose, and prevented the fall in noradrenaline. Doxazosin was largely without effect on any of these parameters. We conclude that i.v. administered alpha-methylnoradrenaline primarily acts on beta-adrenoceptors in the human cardiovascular and metabolic system, but an alpha2-adrenergic component of the response is detectable for changes of plasma noradrenaline, blood glucose, and serum insulin. Whereas alpha-methylnoradrenaline is selective for alpha2- over alpha1-adrenoceptors, beta-adrenoceptor blockade is required to unmask alpha-adrenoceptor-mediated vasoconstriction.     

Do elderly patients with an excessive fall in blood pressure on standing have evidence of autonomic failure?

1. Blood pressure, heart rate and plasma catecholamine responses were examined in two groups of elderly subjects distinguished by blood pressure responses to standing. Subjects in the control group showed a fall of less than 15 mmHg in systolic blood pressure on standing; subjects in the orthostatic hypotension group had falls of more than 20 mmHg systolic and 10 mmHg diastolic blood pressure on standing. 2. The heart pressure response on standing showed no significant difference between the two groups. 3. The orthostatic hypotension patients had lower plasma noradrenaline concentrations than the control patients (P less than 0.01) in the supine position, but during 10 min standing there was no significant difference in noradrenaline levels between the groups, and the percentage increase of noradrenaline levels in the orthostatic hypotension group was greater (P less than 0.05) than in the control group. 4. In the supine position, diastolic blood pressure was higher (P less than 0.05) in the orthostatic hypotension group than in the control group. 5. We conclude that impairment of baroreceptor function is not involved in most cases of orthostatic hypotension in the elderly, nor is there reduction of sympathetic nervous activity. We suggest that mechanical changes or adrenoreceptor dysfunction are more likely to be important factors in orthostatic hypotension in the elderly.     

Clonidine but not propranolol decreases plasma neuropeptide Y (NPY) levels

The effects of acute administration of two antihypertensive drugs, clonidine and propranolol, on plasma NPY and catecholamine levels were compared in sinoaortic denervated (a model associated with a marked increase in sympathetic tone and a rise in blood pressure) and normal conscious dogs. Clonidine decreased plasma noradrenaline and NPY concentrations in both groups of animals. Propranolol failed to change plasma noradrenaline and NPY levels in sinoaortic denervated dogs but elicited a decrease in plasma noradrenaline with no change in NPY levels in normotensive animals. The present experiments show that changes in plasma noradrenaline and NPY concentrations are not always simultaneous. The decrease in plasma NPY concentrations could contribute to the sympatholytic effect of clonidine.     

Renal and cardiovascular effects of caffeine: a dose-response study

The effects of increasing oral doses of caffeine (45, 90, 180 and 360 mg) on effective renal plasma flow (ERPF), plasma renin activity (PRA), serum electrolytes, plasma noradrenaline, blood pressure and heart rate were studied in eight healthy male volunteers. Urine volume was increased by 360 mg of caffeine only. At caffeine doses greater than 90 mg urinary sodium excretion was significantly increased. There were no changes in ERPF. Serum potassium was significantly reduced by 360 mg of caffeine. Caffeine increased systolic pressure in a dose related manner. Diastolic pressure was also increased, but not in relation to dose. A 360 mg dose of caffeine produced a late increase in heart rate. These changes were not associated with any alterations in PRA or in plasma noradrenaline.     

Effects of yohimbine, an α2-adrenoceptor antagonist, on experimental neurogenic orthostatic hypotension

Summary— Yohimbine has been proposed for the treatment of neurogenic orthostatic hypotension; however, no controlled trial has been performed in experimental models of orthostatic hypotension or in patients with autonomic failure. The aim of the present study was to compare the effects of yohimbine (0.05 mg/kg, intravenously [iv]) and placebo (saline) in a new model of neurogenic orthostatic hypotension obtained by sinoaortic denervation (SAD) in chloralose-anaesthetized dogs. Blood pressure, heart rate, noradrenaline plasma levels and systolic blood pressure and heart rate short-term variabilities (calculated on low frequency [40–50 MHz] and high frequency [390–490 MHz] bands) were measured in supine position and after a 10 min 80° head-up tilting. The drugs were administered in a double-blind cross-over randomized fashion. The head-up tilting performed in normal animals increased diastolic blood pressure (+12 ± 4 mmHg), heart rate (+39 ± 12 beats per minute [bpm]), the low frequency band of systolic blood pressure and noradrenaline plasma level, without changing systolic blood pressure or heart rate variability. In SAD dogs, a marked fall in systolic (-80 ± 11 mmHg) and diastolic (-43 ± 4 mmHg) blood pressures was observed within 1 min after placebo, without modification in heart rate, systolic blood pressure and heart rate short-term variabilities and noradrenaline plasma levels. In SAD dogs, yohimbine (0.05 mg/kg, iv) delayed the blood pressure fall elicited by head-up tilting, but failed to modify its magnitude. These results show that, in the model of orthostatic hypotension obtained by SAD, yohimbine, at an α₂-adrenoceptor selective dose (0.05 mg/kg), delays the fall in blood pressure elicited by head-up tilting. The effect of yohimbine can be explained by an increase in sympathetic tone.     

Effects of meal composition on the postprandial blood pressure, catecholamine and insulin changes in elderly subjects

1. The effects of four meals of similar energy, but different nutritional, composition on postprandial blood pressure, heart rate, autonomic function, catecholamines, insulin and packed cell volume levels were studied in seven fit elderly subjects. 2. The high carbohydrate and high protein meals led to a significant overall fall in supine systolic and diastolic blood pressure compared either with no change or a rise after the normal (i.e. mixed) and high fat meals. Similar between-meal differences were seen with erect diastolic but not erect systolic blood pressure. No significant postural blood pressure fall occurred after any of the meals. Supine heart rate was unaffected by meal type or by time, and although erect heart rate showed a small increase during the study there was no between-meal difference. 3. Parasympathetic function was unaffected by meal type. Plasma noradrenaline rose after the high carbohydrate and mixed meals only, remaining elevated for 120 min after meal consumption. This increase was not related to the changes in blood pressure or plasma insulin levels. 4. Plasma insulin and glucose rose after the high carbohydrate and mixed meals, but were unchanged after the high protein and high fat meals. Packed cell volume showed a small decrease towards the end of the study, although there was no between-meal variation. 5. The differences in the cardiovascular changes after the different meals could not be ascribed to alterations in autonomic function, insulin release or fall in plasma volume. We propose that the postprandial changes in blood pressure are due to the nutrient composition of the meal rather than the actual energy load.     

Arterial and venous plasma catecholamines during submaximal steady-state exercise

Arterial and venous plasma catecholamine responses to 15 min of cycling at 60% of maximal oxygen uptake were examined 11 times during exercise and recovery in nine young men. Intra-arterial blood pressure, heart rate and oxygen uptake were recorded continuously. All variables increased significantly during the initial 4 min, after which oxygen uptake, diastolic blood pressure and arterial plasma adrenaline showed no further increase. Heart rate and plasma noradrenaline, however, continued to increase, although significantly more slowly, and were closely correlated (r = 0·81, 95% CI 0·71–0·87), as were systolic blood pressure and heart rate (r = 0·78, 95% CI 0·71–0·87). Venous plasma adrenaline showed a steady increase during the whole exercise period and thus a different response pattern from arterial plasma adrenaline. In conclusion, arterial plasma catecholamines respond to steady-state exercise by a two-phase pattern paralleling the changes in arterial blood pressure and heart rate. Venous sampling does not reveal this association.     

Changes in plasma free 3,4-dihydroxyphenylethylene glycol and noradrenaline levels after acute alcohol administration

The effects of alcohol (0.9 g/kg) compared with placebo (400 ml of orange juice) on plasma noradrenaline and 3,4-dihydroxyphenylethylene glycol levels, and on erect and supine blood pressures and heart rates, were studied in eight normal male volunteers. Alcohol caused a rise in noradrenaline levels that commenced approximately 30 min after drinking and lasted about 4 h. In contrast, 3,4-dihydroxyphenylethylene glycol levels fell immediately after alcohol administration and remained low for at least 6 h. Acute alcohol administration alters noradrenaline catabolism, and may have a dual effect of increasing noradrenaline release and decreasing noradrenaline clearance. Alcohol caused a transient rise in erect and supine blood pressures that preceded the rise in plasma noradrenaline. Thereafter erect blood pressures fell compared with control. This fall was associated with a progressive rise in both supine and erect rates, and reached a maximum several hours after the maximum levels of blood alcohol. The major effect of acute alcohol administration is to lower blood pressure and induce a reflex tachycardia. Changes in noradrenaline and 3,4-dihydroxyphenylethylene glycol levels did not readily explain changes in blood pressure or heart rate, suggesting that alcohol induced changes in noradrenaline metabolism occur largely independent of changes in blood pressure and heart rate.     

Side-effects of L-dopa on venous tone in Parkinson's disease: a leg-weighing assessment

In the present study, the effects of L-dopa treatment on cardiovascular variables and peripheral venous tone were assessed in 13 patients with Parkinson's disease (PD) with Hoehn and Yahr stages 1-4. Patients were investigated once with their regular treatment and once after 12 h of interruption of L-dopa treatment. L-Dopa intake significantly reduced systolic and diastolic blood pressure, heart rate and plasma noradrenaline and adrenaline in both the supine and upright (60 degrees ) positions. A significant reduction in stroke volume and cardiac output was also seen with L-dopa. The vascular status of the legs was assessed through thigh compression during leg weighing, a new technique developed in our laboratory. Healthy subjects were used to demonstrate that this technique provided reproducible results, consistent with those provided by strain gauge plethysmography of the calf. When using this technique in patients with PD, L-dopa caused a significant lowering of vascular tone in the lower limbs as shown, in particular, by an increase in venous distensibility. Combined with the results of the orthostatic tilting, these findings support that the treatment-linked lowering of plasma noradrenaline in patients with PD was concomitant with a significant reduction in blood pressure, heart rate and vascular tone in the lower limbs. These pharmacological side-effects contributed to reduce venous return and arterial blood pressure which, together with a lowered heart rate, worsened the haemodynamic status.     

Oscillations of cerebrovascular resistance throughout the menstrual cycle in healthy women.

OBJECTIVES: Increased concentration of endogenous estrogen during a typical menstrual cycle has been shown to correlate with augmentation of blood flow through the internal carotid arteries (ICAs), which may be related to changes in vascular resistance within the brain. In this study we investigated the effects of endogenous estrogen and progesterone on cerebrovascular impedance in young healthy women. METHODS: The blood flow in the ICA and the common (CCA) and external (ECA) carotid arteries was studied with duplex Doppler sonography. The resistance index (RI) was determined and correlated with plasma 17beta-estradiol concentration in 14 young healthy women throughout their menstrual cycle. RESULTS: The concentration of 17beta-estradiol increased in the follicular phase of the cycle and reached a peak on day 14, whereas concentration of progesterone remained low. Along with an increase in estrogen concentration, the ICA RI had decreased from its initial level on average by 9.2% on day 13 and by 6.7% on day 14 (P < 0.05). In contrast, the trend of the ECA RI was to increase during the peak of estrogen concentration. There were no significant changes in the CCA RI or in the systolic blood pressure, heart rate, hematocrit and hemoglobin concentration through the menstrual cycle. CONCLUSIONS: Estrogen-related augmentation of blood flow through the ICA is caused mainly by decreased cerebrovascular impedance, as shown by a decrease in the ICA RI. These changes in RI suggest that estrogen influences cerebral impedance mainly by altering the resistance of cerebral microvasculature.     

Multifactorial evaluation of blood pressure fall upon hospitalization in essential hypertensive patients

1. Studies were prospectively performed on 72 hospitalized patients with essential hypertension. Blood pressure was normalized within 1 week of admission in 33 patients (group I), but did not decrease in 39 patients (group II). To determine the factors that differentiate group I from group II, cardio-renal haemodynamic and endocrinological indices were evaluated using multivariate analysis. 2. Systolic, diastolic and mean blood pressures on admission were higher in group II (P less than 0.001), whose optic fundi showed more severe changes (P less than 0.001). Although group II had greater left ventricular posterior wall thickness (P less than 0.02), left ventricular mass index (P less than 0.05) and systemic vascular resistance (P less than 0.01) on echocardiography, their cardiac index and ejection fraction were comparable with those of group I. 3. Renal blood flow (P less than 0.05) and glomerular filtration rate (P less than 0.01) were lower in group II than in group I. Renal vascular resistance was more elevated (P less than 0.01) in group II than in group I. 4. After severe sodium depletion and ambulation, group I showed a greater increase in plasma noradrenaline and adrenaline (P less than 0.05). On multivariate analysis, those with lower systolic blood pressure, better renal function and more reactive sympathetic nervous system were discriminated as group I. 5. These data suggest that group I patients have lower systolic blood pressure on admission, greater sympathetic reactivity and better renal function, all of which contribute to their spontaneous blood pressure fall after admission.     

Plasma Catecholamines and Carbohydrate Metabolism in Patients with Acute Myocardial Infarction

Blood glucose, glucose tolerance, serum insulin, free fatty acids in serum, plasma noradrenaline, and plasma adrenaline were measured in 10 patients with acute myocardial infarction (AMI) as well as in healthy subjects. Both noradrenaline and adrenaline in plasma were elevated in patients with AMI, the level being fairly constant in the individual patients and dependent on their degree of illness.In the fasting state, blood glucose, serum insulin, and free fatty acids were elevated in patients with AMI. Plasma noradrenaline showed a highly significant correlation with the fasting blood glucose concentration, but not with serum insulin or free fatty acids. The concentration of free fatty acids in serum could be predicted only if both plasma noradrenaline and the basal insulin concentration were known.Intravenous glucose tolerance was reduced in patients with AMI, especially in patients with high plasma noradrenaline and a low initial rise in insulin. There was a significant negative correlation between the initial rise in insulin expressed in percentage of the basal insulin concentration and the plasma noradrenaline level. The statistical effects of serum insulin and plasma noradrenaline on the glucose tolerance could not be separated from each other. The decline in free fatty acids after intravenous injection of glucose showed a negative correlation with plasma noradrenaline and a positive correlation with the initial rise in insulin.Plasma adrenaline did not correlate with any of the metabolic parameters mentioned above.The plasma noradrenaline concentration was elevated to such a degree in patients with AMI that the observed changes in metabolism might have been caused directly by the circulating noradrenaline.During the glucose tolerance tests, the effects of noradrenaline was probably carried out indirectly via a suppression of insulin secretion. It is conceivable that any effect of plasma noradrenaline on the basal insulin secretion was neutralized by the fasting hyperglycemia.     

Effect of exercise training on plasma catecholamines and haemodynamics of adolescent hypertensives during rest,submaximal exercise and orthostatic stress

Summary. Twelve adolescents with essential hypertension were studied to determine the effect of exercise training on plasma catecholamine concentrations, blood pressure and cardiovascular haemodynamics at rest and during submaximal exercise and orthostatic stress. Maximal oxygen consumption (V?O₂max) increased 13% with training while body weight and body fat did not change. Resting systolic and diastolic blood pressures decreased significantly with training, while plasma norepinephrine and epinephrine levels were unchanged. The increase in systolic blood pressure in response to standing was significantly lower after training, while the plasma catecholamine response was not significantly different. At the same absolute work rate after training, the subjects' systolic and diastolic blood pressures, heart rates, and plasma norepinephrine and epinephrine levels were significantly lower than before training. At the same relative work rate after training, the blood pressure response was the same as before training despite significantly higher plasma norepinephrine levels. Thus, the training-induced changes in resting blood pressures and blood pressure responses to orthostatic and submaximal exercise stress cannot be attributed to decreases in plasma catecholamine levels.     

Portal blood flow in man during graded positive end-expiratory pressure ventilation

The cardiovascular response to graded PEEP ventilation (5–10 cm H₂O) was studied peroperatively in patients undergoing chllecystectomy (n=8) or hepatic tumour surgery (n=3). Portal blood flow was measured by the continuous thermodilution technique and cardiac output, in a sub-group of the patients, by impedance cardiography. A parallel reduction in cardiac output and portal blood flow was demonstrated in patients undergoing cholecystectomy as the result of the application of PEEP. Thus, ventilation with 5 cm H₂O of PEEP elicited a 17% decrease in cardiac output and a 26% decrease in portal blood flow. During 10 cm H₂O of PEEP cardiac output decreased by 22% and portal blood flow by 32%. However, there were no significant changes in preportal tissue perfusion pressure by the application of PEEP and preportal vascular resistance increased by 22% and 30%, respectively. This indicates that a vasoconstrictor response, elicited by PEEP, in the preportal tissue is the predominating mechanism for the observed decrease in portal blood flow. Systemic oxygen transport decreased by 214 ml/min during PEEP ventilation, but preportal tissue oxygen utilization was not significantly changed due to a concurrent increase (2.9%; p<0.05) in oxygen extraction.     

Rate Response of a Closed-Loop Stimulation Pacing System to Changing Preload and Afterload Conditions

Closed-loop stimulation (CLS) is a new sensor concept for rate adaptive pacing measuring changes in the unipolar right ventricular impedance, which correlates to changes of the right ventricular contractility and reflects the autonomic nervous innervation of the heart. Some patients do not tolerate the CLS mode because of inappropriate tachycardia, mainly related to postural changes. This study tested if the rate response of the CLS sensor is influenced not only by myocardial contractility but also by rapid changes in right ventricular filling. In 12 patients (10 men, median age 77 years) with a Biotronik Inos²-CLS DDDR pacemaker and 14 controls (13 men, median age 59 years) head-up tilt and handgrip testing was performed to provoke rapid changes in pre- and afterload. Tilting the pacemaker patients resulted in a nonphysiological steep increase of the sensor rate (increase >20 beats/min, peak after 1 minute, return to baseline within 2–3 minutes), which was significantly different from the control group, showing only a slight rise in intrinsic heart rate immediately after tilting. Simultaneously to the rapid increase in sensor rate, the pacemaker patients showed a marked orthostatic decline of systolic blood pressure. During handgripping, heart rate and blood pressure curves were similar in both groups. In patients with this CLS pacemaker, rapid preload reduction during head-up tilting caused an overshooting sensor rate increase, reproducing the authors' clinical observation of postural pacemaker tachycardia in some patients. Consequently, they concluded that the rate response of the CLS pacing system can be inappropriately influenced by rapid shifts of blood volume, affecting right ventricular filling. (PACE 2003; 26[Pt. I]:1504–1510)     

Effect of molsidomine on hemodynamics in patients with dilated cardiomyopathy

The effect of 4 mg Molsidomine iv. followed by a continuous infusion of 3 mg per hour for 3 hours on arterial blood pressure, pulmonary artery pressure, cardiac index, peripheral and pulmonary vascular resistance and heart rate was evaluated in eleven patients suffering from chronic heart failure caused by non-ischaemic dilatative cardiomyopathy (NYHA II-III). A significant decrease in systemic blood pressure, systolic and mean pulmonary artery pressure and pulmonary wedge pressure was observed and also a marked decrease in total peripheral and pulmonary vascular resistance. There was a slight, but not significant increase in cardiac index. The heart rate did not change significantly. Treatment had to be stopped in one patient because of side effects (hypotension, nausea).     

An experimental study of cardiac natriuretic peptides as markers of development of congestive heart failure

The use of cardiac peptide measurements as possible diagnostic tools in congestive heart failure has been extensively discussed in the recent literature. Therefore, the aim of this study was to establish a model of experimental chronic heart failure, and thereby perform a comparative study of secretion and circulating levels of the cardiac peptides atrial natriuretic peptide (ANP), N-terminal proatrial natriuretic peptide (N-terminal proANP) and brain natriuretic peptide (BNP) during evolving heart failure. Chronic heart failure was induced in seven pigs by rapid left atrial pacing for three weeks. The effects of failure induction were documented 24 h after pacemaker deactivation. Hemodynamic indices of cardiac preload, like pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP), were all considerably increased compared to sham operated controls. Likewise, plasma endothelin-1, noradrenaline, renin activity, aldosterone and angiotensin II were all markedly increased. Heart failure was accompanied by significant increases in both estimated cardiac secretory rate and plasma concentrations of all three cardiac peptides, significantly correlated to the PCWP. The directional changes during evolving heart failure were similar, although the percentage increase in plasma BNP was much larger than for ANP and N-terminal proANP. In absolute molar terms, however, the BNP concentration changes were minor compared to those of the other two peptides. The larger percentage increase of BNP might indicate its superiority as a marker of heart failure development, provided a functional assay suitable for clinical use can be designed for a peptide circulating in this low concentration range.