Increase In Plasma Catecholamines Research Articles

Renal response to hypoxia in carp, Cyprinus carpio: Changes in glomerular filtration rate, urine and blood properties and plasma catecholamines of carp exposed to hypoxic conditions

1. 1. Changes in glomerular nitration rate (GFR), urine and blood properties and plasma catecholamines of carp were investigated during and following hypoxia. 2. 2. GFR and urine flow decreased with increased urinary concentrations of bio-components, except protein, in the course of hypoxia. 3. 3. Decreases in blood pH, and increases in haematocrit value and plasma K +, Ca 2+, Mg 2+, inorganic phosphate (P i), ammonia, lactic acid and catecholamines (CAs) were observed as hypoxia progressed. 4. 4. Increased GFR and urine flow, and higher values for urinary components, except protein, compared with those of the control were found in the initial post-stress stage. 5. 5. The possible significance of increased plasma CAs in relation to changes in renal function in hypoxic carp is discussed.

Mental stress and cognitive performance do not increase overall level of cerebral O2 uptake in humans.

We measured cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF), and cerebral lactate output during rest, during the execution of mental arithmetic, and during mental stress induced by physical and psychological annoyance. Measurements were performed in healthy volunteers by use of the Kety-Schmidt technique with 133Xe as the inert gas. Electroencephalographic desynchronization and highly significant increases in plasma catecholamines and heart rate verified that the test measurements were performed during conditions differing distinctly from the resting state. In accordance with an earlier study (Sokoloff et al. J. Clin. Invest. 34: 1101-1108, 1985), a minimal and nonsignificant 1% reduction of global CMRO2 during mental arithmetic was observed, signifying that this form of mental activation was unassociated with any detectable increase in overall cerebral synaptic activity. Mental stress induced a slight but highly significant (P less than 0.002) 6% reduction in global CMRO2. This finding is in contrast to results from earlier investigations and contradicts the generally accepted notion of an association between mental arousal and a diffuse upregulation of cerebral synaptic activity. During mental arithmetic and mental stress, cerebral lactate output increased by 207 and 344%, respectively, but because of large individual variations in the measured responses, the elevations reached statistical significance only during mental arithmetic.

Hypertension in the elderly with a special focus on treatment with angiotensin-converting enzyme inhibitors and calcium antagonists

Age-related changes (e.g., decrease in plasma rental activity and total body potassium, increase in plasma catecholamines, volume depletion) need to be taken into account when selecting an airtihypertensive agent for the elderly patient. A number of large scale clinical trials (e.g., Systolic Hypertension in the Elderly Program, Veterans Administration Cooperative Study, European Working Party on High Blood Pressure in the Elderly) have demonstrated that antihypertensive therapy with diuretics substantially reduces cardiovascular mortality and stroke incidence. However, since diuretics, even potassium-sparing agents, may induce hypokalemia, newer antihypertensive agents (angliotensin-converting enzyme [ACE]inhibitors and calcium antagonists) may also be appropriate as first-line monotherapy for this patient population. ACE inhibitors are effective antihypertensive agents and are associated 3 with a lower rate of adverse effects than diuretics, β blockers, and centrally acting agents. Nevertheless, periodic monitoring of serum potassium, creatinine levels, and renal function is advisable. An important feature of calcium antagonists is that they lower blood pressure with no negative effect on serum lipids or glucose metabolism. Typically, they have few side effects, peripheral edema being the most commonly reported. A recent double-bind randomized study comparing a new sustained release nifedipine formulation and the ACE inhibitor lisinopril found the 2 drugs equivalent in efficacy with no differences in the rate of adverse events.

Beta-Adrenoceptor Modulation in a Case of Pure Autonomic Failure

In a patient with pure autonomic failure, exercise did not modify beta-adrenoceptor density, probably due to an insufficient increase in plasma catecholamines. Isoproterenol infusion increased the number of beta-adrenoceptor by only 17%. Since in control subjects an increased beta-adrenoceptor level was found, following both physical stress and isoproterenol infusion, we suggest that the lack of increased beta-adrenoceptor levels may contribute to the poor circulatory adjustments observed in autonomic dysfunction during activities involving the sympathetic nervous system.

Awareness of high blood pressure influences on psychological and sympathetic responses

The aim of the present study was to examine the effects of awareness of hypertension on psychological factors and whether there was an association between psychological and sympathetic responses. To avoid self-selection bias 32 19-yr old white men, all with mean blood pressure of 116 mm Hg were randomized into two groups. One group was informed that the blood pressure was elevated and asked to come to a second examination while the other was invited to take part in a coronary heart disease prevention program. A cold pressor test was undertaken and the subjects completed the Karolinska Scale of Personality (KSP). Assessed by the KSP, the informed group showed lower verbal aggression ( p < 0.01), irritability ( p < 0.05), monotony avoidance ( p < 0.05) and impulsiveness ( p < 0.05), higher detachment ( p < 0.05) but no significant differences in the other subscales like anxiety, psychasthenia or factors of hostility. Information significantly increased resting blood pressure and increments in heart rate and plasma adrenaline responses to cold pressor test. Thus, both psychological and sympathetic responses were influenced by awareness of high blood pressure. There were significant correlations between less assertive behaviour and increased plasma catecholamines.

Plasma 19-hydroxy-androstenedione (19-OH-A) in essential hypertension.

19-hydroxy-androstenedione (19-OH-A), a C19 steroid, is an amplifier of the sodium retaining action of aldosterone under the control of ACTH and renin-angiotensin system. These findings suggest that 19-OH-A may be involved in the regulation of hydroelectrolyte balance and blood pressure. Aim of the present study was to examine the behaviour of 19-OH-A in normal volunteers (N) and in patients with Essential Hypertension (EH) in basal conditions and after dynamic tests such as postural changes, physical exercise and ACTH administration. The significant increase in 19-OH-A after ACTH confirms its adrenal origin. During bicycle exercise the significant increase in plasma catecholamines, renin-activity, aldosterone, blood pressure and heart rate at maximum effort was not associated with a parallel increase in 19-OH-A. No significant differences were found in plasma 19-OH-A levels between N and EH patients both in basal conditions and after dynamic tests. Therefore, our findings seem to exclude an important role of 19-OH-A in the pathogenesis of EH.

Collagen-induced Platelet Activation In Vitro Increases Plasma Catecholamine Concentration

Collagen-induced Platelet Activation In Vitro Increases Plasma Catecholamine Concentration

A mechanism of catecholamine tolerance in congestive heart failure--alterations in the hormone sensitive adenylyl cyclase system of the heart.

It is well known that failing hearts show diminished responsiveness (desensitization) to catecholamines. In this study, 2 different animal models were used to investigate the alterations in the hormone sensitive cardiac adenylyl cyclase system in a congestive heart failure. In the first model, cardiomyopathic Syrian hamsters (BIO53.58), we found reduced activity of the catalytic protein of adenylyl cyclase; this reduction was more prominent in an older animals (28-week-old vs 16-week-old). At both ages, the amount of inhibitory GTP-binding protein (Gi) was markedly increased in BIO53.58 compared to control healthy hamsters. Moreover the increased Gi was shown to be fully functional in the inhibitory pathway of the adenylyl cyclase system. In the second model, chronically norepinephrine-infused rats, we found a decrease in beta-adrenergic receptor density at an early stage of injection (3 days), while the activity of catalytic protein decreased beyond 14 days of injection, and the amount of Gi increased after 7 days of injection. These results suggest that increased plasma catecholamine concentrations in the setting of congestive heart failure might be a major trigger for qualitative and quantitative alterations observed in various components of cardiac adenylyl cyclase system, and that GTP-binding proteins and catalytic protein of adenylyl cyclase are involved in the mechanism of desensitization especially after chronic in vivo stimulation of adrenergic receptors.

Beta-adrenoceptor stimulation-induced increase in cardiac Gi-protein expression and in carbachol sensitivity

Increased plasma concentrations of catecholamines are assumed to be responsible for the decreased sensitivity to catecholamines of the failing heart. We investigated in rat heart the influence of a 4-day infusion of isoprenaline (Iso; 2.4 mg.kg-1.d-1), propranolol (Prop; 9.9 mg.kg-1.d-1), Iso + Prop or 0.9% NaCl as control (Ctr) on myocardial Gi-mRNA and Gi-protein levels and on the negative inotropic effect of carbachol in papillary muscles. In Iso-treated rats, hybridization experiments with 32P-cDNAs revealed a 49 +/- 18% (n = 7-8) and 27 +/- 7% (n = 8) increase in Gi alpha-2- and Gi alpha-3-mRNA respectively, and pertussis toxin-catalyzed ADP-ribosylation revealed a 22 +/- 7% (n = 8) increase in Gi-protein as compared to Ctr. These alterations were accompanied by an increased potency of carbachol (mean EC50: 0.04 microM vs. 0.28 microM) in the presence of Iso in isolated electrically driven (1 Hz) papillary muscles. Prop had no effect on Gi-protein expression but antagonized all Iso-induced effects. In conclusion, beta-adrenergic stimulation leads to an increased expression of Gi and to an enhanced negative inotropic potency of muscarinic agonists. An enhanced muscarinic receptor coupling via Gi might play a pathophysiological role in heart diseases with increased plasma catecholamine levels.

Disabling Postural Hypotension Complicating Diabetic Autonomic Neuropathy

A 35-year-old Type 1 diabetic man with severe disabling postural hypotension was studied for physiological abnormalities, precipitating factors, and effect of current treatment. A 24-h blood pressure profile indicated a diurnal variation in systolic blood pressure with the lowest values recorded between 0100 and 0600 h, during which the patient often lost consciousness on standing (mean standing systolic pressure 78 mmHg at night vs 105 mmHg in the afternoon, p less than 0.001). Food induced a profound fall in systolic pressure, both while supine and while standing erect. The systolic pressure fall during euglycaemia was 49 mmHg vs 3 mmHg during hypoglycaemia. Plasma noradrenaline and adrenaline levels were low during euglycaemia, but increased during hypoglycaemia. Therapeutic manoeuvres aimed at increasing heart rate (by atrial tachypacing) and reducing the peripheral pooling of blood (vasoconstricting drugs and gravity suit), together with the somatostatin analogue octreotide, proved ineffective. These observations demonstrate the phenomenon of post-prandial exacerbation of postural hypotension in a Type 1 diabetic patient, and indicate that despite failure of conventional methods of treatment, hypoglycaemia increased plasma catecholamines and was effective in abolishing the blood pressure fall on standing.

Skeletal Muscle Blood Flow and O2 Uptake During Intravenous Nicotine With and Without Hypertension

The mechanism by which nicotine causes peripheral vasoconstriction and its relationship to the increased risk of peripheral vascular disease in smokers are unknown. To study the peripheral vascular effects of nicotine, we measured hemodynamic responses and oxygen consumption of the in situ gracilis muscle during intravenous (i.v.) nicotine infusions in anesthetized dogs. Nicotine 36.0 micrograms/kg/min increased gracilis artery pressure (Pga) 91 +/- 17% and muscle vascular resistance (MVR) 96 +/- 18% whereas muscle blood flow (MBF) and oxygen consumption (MVO2) were unchanged from baseline. In dogs with extracorporeal-controlled normotension during nicotine infusion, however, Pga was held at baseline levels but similar increases in MVR were observed (95 +/- 11%) as flows decreased 52 +/- 9%. Oxygen consumption decreased in direct proportion (53 +/- 5%) to MBF, indicating complete impairment of oxygen extraction (A-VO2). Thus impaired oxygen extraction was masked in dogs in which Pga was allowed to increase because of sustained pressure-dependent flows. Phenoxybenzamine block of muscle alpha-adrenoceptors increased MBF and MVO2 in both normotensive and hypertensive dogs. Combined alpha- and beta-blockade effectively neutralized all sympathoadrenal responses in the muscle. All the above results occurred regardless of innervation. Plasma levels of norepinephrine (NE) and epinephrine (EPI) increased greater than 1,000% during nicotine infusion. Apparently, these levels were high enough to (a) override dilator effects of plasma EPI and (b) cause vasoconstriction in muscle independent of nerve supply. Infusion of nicotine in the gracilis artery had no effect on muscle hemodynamics. Nicotine-induced increase in plasma catecholamines resulted in a powerful constriction of both resistance and oxygen-exchange vessels of skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Potassium regulation during exercise and recovery.

The concentrations of extracellular and intracellular potassium (K+) in skeletal muscle influence muscle cell function and are also important determinants of cardiovascular and respiratory function. Several studies over the years have shown that exercise results in a release of K+ ions from contracting muscles which produces a decrease in intracellular K+ concentrations and an increase in plasma K+ concentrations. Following exercise there is a recovery of intracellular K+ concentrations in previously contracting muscle and plasma K+ concentrations rapidly return to resting values. The cardiovascular and respiratory responses to K+ released by contracting muscle produce some changes which aid exercise performance. Increases in the interstitial K+ concentrations of contracting muscles stimulate CIII and CIV afferents to directly stimulate heart rate and the rate of ventilation. Localised K+ release causes a vasodilatation of the vascular bed within contracting muscle. This, together with the increase in cardiac output (through increased heart rate), results in an increase in blood flow to isometrically contracted muscle upon cessation of contraction and to dynamically contracting muscle. This exercise hyperaemia aids in the delivery of metabolic substrates to, and in the removal of metabolic endproducts from, contracting and recovering muscle tissues. In contrast to the beneficial respiratory and cardiovascular effects of elevations in interstitial and plasma K+ concentrations, the responses of contracting muscle to decreases in intracellular K+ concentrations and increases in intracellular Na+ concentrations and extracellular K+ concentrations contribute to a reduction in the strength of muscular contraction. Muscle K+ loss has thus been cited as a major factor associated with or contributing to muscle fatigue. The sarcolemma, because of changes in intracellular and extracellular K+ concentrations and Na+ concentrations on the membrane potential and cell excitability, contributes to a fatigue 'safety mechanism'. The purpose of this safety mechanism would be to prevent the muscle cell from the self-destruction which is evident upon overload (metabolic insufficiency) of the tissues. The net loss of K+ and associated net gain of Na+ by contracting muscles may contribute to the pain and degenerative changes seen with prolonged exercise. During exercise, mechanisms are brought into play which serve to regulate cellular and whole body K+ homeostasis. Increased rates of uptake of K+ by contracting muscles and inactive tissues through activation of the Na(+)-K+ pump serve to restore active muscle intracellular K+ concentrations towards precontraction levels and to prevent plasma K+ concentrations from rising to toxic levels. These effects are at least partially mediated by exercise-induced increases in plasma catecholamines, particularly adrenaline.(ABSTRACT TRUNCATED AT 400 WORDS)

The α2-adrenergic receptor antagonist yohimbine inhibits epinephrine-induced platelet aggregation in healthy subjects

Onset of sudden death, myocardial infarction, and stroke occurs more likely in the morning hours. Similarly, a morning increase in epinephrine-induced platelet aggregation was observed accompanied by an increase in plasma catecholamines. Inhibition of the morning increase in platelet aggregation would be of therapeutic benefit. In this study the effect of the selective alpha 2-adrenergic receptor antagonist yohimbine on platelet aggregation was evaluated in healthy subjects. Yohimbine administered orally selectively antagonized epinephrine but not collagen, arachidonic acid, or adenosine diphosphate-induced ex vivo platelet aggregation. The lowest dose of yohimbine that significantly inhibited epinephrine-induced platelet aggregation was 8 mg. The inhibitory effect of yohimbine on platelet aggregation lasted 10 hours with the 12 mg dose. At the doses studied (4, 8, and 12 mg), yohimbine did not modify blood pressure, standing heart rate, or plasma catecholamine or glucose concentrations. Twelve milligrams of yohimbine moderately but significantly accelerated supine heart rate (mean maximal increase, 7 +/- 3 beats/min). Further clinical studies are needed to evaluate whether bedtime administration of 12 mg yohimbine may block the morning increase in epinephrine-induced platelet aggregation.

Plasma catecholamines and oxygen consumption during weaning from mechanical ventilation

Previous studies on oxygen consumption (VO2) during weaning from mechanical ventilation assumed that an increase in VO2 (delta VO2) reflected oxygen consumption by respiratory muscles (VO2RESP), and proposed delta VO2 as a weaning predictor. We measured VO2 CO2 production (VCO2) and plasma catecholamines in 20 short-term ventilated patients during weaning by SIMV and CPAP. delta VO2 as a percentage of VO2 during spontaneous ventilation (delta VO2%) ranged from 4.8% to 41.5%. VCO2 also increased and correlated with VO2. Plasma adrenaline and noradrenaline increased significantly to levels known to produce considerable increases in metabolic rate. Mean arterial pressure and heart rate concomitantly increased, but spontaneous minute ventilation decreased. Thus, since the increased plasma catecholamines are calorigenic, the assumption that delta VO2 represents VO2RESP is incorrect. Although mean delta VO2% of successfully weaned patients was significantly less than that of failure-to-wean patients, the wide scatter of individual values in the latter group excludes delta VO2% as an accurate weaning predictor.

Sympathoadrenal activation in sinoaortic-denervated rats following endotoxin

We evaluated the role of the baroreceptor reflex in mediating the sympathoadrenal activation during endotoxicosis, using acutely as well as chronically denervated rats. Three groups of experiments were conducted. In the first experiment, hemodynamic and plasma catecholamine responses following endotoxin (5 mg/kg iv) were measured in alpha-chloralose-anesthetized rats with acute sinoaortic baroreceptor denervation (SAD) or sham operation. In the second experiment, chronically sinoaortic-denervated rats and sham controls were used and experiments were conducted as in acute preparations. In the third experiment hydralazine (1 mg/kg iv) was given to chronically denervated rats and sham controls to evaluate the singular contribution of hypotension-evoked baroreflex disinhibition in the absence of endotoxin. In both acute and chronic preparations, endotoxin induced marked elevation of plasma norepinephrine and epinephrine in the presence as well as the absence of arterial baroreceptors (P greater than 0.05). Plasma catecholamines were significantly increased by hydralazine-induced hypotension in the sham group, but this elevation was far less than that induced by endotoxin. Hypotension alone did not significantly increase plasma catecholamines in SAD rats. These results suggest that the baroreflex is not the major factor in mediating sympathoadrenal activation during endotoxicosis and that non-baroreflex mechanisms may be involved in stimulating such activation.

Hemodynamic effects of nicotine in canine skeletal muscle.

Studies were conducted in 36 artificially ventilated, anesthetized dogs to clarify hemodynamic effects of nicotine in resting gracilis muscle. In Series 1, effects of intravenous nicotine (36 micrograms/kg/min) were evaluated in (i) intact muscles (Condition 1), (ii) denervated muscles (Condition 2), (iii) denervated muscles following local alpha-adrenergic blockade (Condition 3), (iv) denervated muscles following combined local alpha- and beta-adrenergic blockade (Condition 4), and (v) intact muscles with aortic pressure maintained constant (Condition 5). In Series 2, nicotine was infused directly into the gracilis artery at a rate of 3.6 micrograms/kg/min. Muscle blood flow was obtained with an electromagnetic flowmeter and used to calculate vascular resistance and oxygen consumption (Fick equation). Plasma catecholamine levels were determined with a radioenzymatic method. Intravenous nicotine doubled mean aortic pressure under Conditions 1-4. In intact and denervated muscles (Conditions 1 and 2) proportional increases in vascular resistance, reflective of vasoconstriction, held blood flow constant. Muscle oxygen consumption was unchanged. alpha-Adrenergic blockade with phenoxybenzamine following denervation (Condition 3) converted muscle vasoconstriction to vasodilation during nicotine infusion. Additional beta-adrenergic blockade (Condition 4) restored muscle vasoconstriction. Nicotine-induced muscle vasoconstriction was maintained under controlled pressure (Condition 5). Intravenous nicotine significantly increased plasma catecholamine levels. Intra-arterial infusions of nicotine (Series 2) caused no hemodynamic changes in muscle. In conclusion, intravenous nicotine caused vasoconstriction in muscle, which was not due to reduced metabolic demand, pressure-flow autoregulation, or a direct [corrected] effect on vascular smooth muscle, but to stimulation of alpha-adrenergic receptors. Following denervation, this vasoconstriction was maintained by elevated plasma catecholamines. alpha-Adrenergic blockade unmasked nicotine-induced vasodilation mediated by beta-adrenergic receptors, whereas combined alpha- and beta-adrenergic blockade unmasked nicotine-induced vasoconstriction by a nonadrenergic mechanism.

Ventilatory and Cardiovascular Responses to Blood pH, Plasma Pco2, Blood O2Content, and Catecholamines in an Air-Breathing Fish, the Bowfin (Amia calva)

Hydrochloric acid (HCl) infusion during aquatic normoxia increased blood pressure, gill ventilation, and air breathing in bowfin. These responses were associated with a reduction in arterial blood pH (pHa) and O2, content (Cao2) and an increase in arterial plasma CO2 tension (Paco2). Ammonium bicarbonate (NH4HCO3) infusion did not change pHa or Cao2 but increased Paco2 and had no effects on blood pressure or ventilation. In aquatic hyperoxia, HCl infusion lowered pHa and Cao2. Arterial blood O2 content, however, was maintained above normoxic levels, and there were no cardiovascular or ventilatory responses. These results indicate that cardiovascular and ventilatory responses to acid-base disturbances in bowfin are correlated with reductions in Cao2 below normoxic levels and not with decreases in pHa or increases in Cao2. Hydrochloric acid infusion in normoxia stimulated a release of endogenous catecholamines, whereas NH4HCO3 infusion and HCl infusion in hyperoxia did not. Catecholamine infusion stimulated gill ventilation but not air breathing. The correlation between increases in plasma catecholamines and gill ventilation following HCl infusion in normoxia indicates that circulating catecholamines may contribute to gill ventilatory responses to hypoxemia in bowfin.

Comparison of two doses of endotracheal epinephrine in a cardiac arrest model

The objective of this study was to measure plasma catecholamine levels and the cardiovascular response before and after endotracheal administration of epinephrine in a swine cardiac arrest model. Prospective, controlled laboratory investigation. Twenty-one swine weighing 10 to 12 kg, anesthetized with ketamine and alpha-chloralose and ventilated with room air. Ventricular fibrillation was induced with 90 V of 60 Hz current delivered to the right ventricle by transvenous pacemaker. Blood samples for epinephrine were drawn before arrest and every two minutes thereafter. At five minutes, external mechanical cardiac compressions were initiated. Nine animals received no further therapy and served as controls. Two groups of six animals received either 0.01 mg/kg or 0.1 mg/kg of epinephrine through the endotracheal tube at ten and 20 minutes. Blood samples were assayed for epinephrine. Arterial blood pressure, lead II ECG, and plasma epinephrine. Swine receiving epinephrine 0.01 mg/kg had an increase in epinephrine levels after drug administration, but these were not significantly different from control levels. The 0.1-mg/kg dose group had a significant increase in plasma epinephrine levels compared with controls and the 0.01-mg/kg dose group after receiving epinephrine at ten and 20 minutes. These increases were from 14 +/- 3 to 215 +/- 40 ng/mL (+/- SEM) at 12 minutes after arrest and from 151 +/- 56 to 402 +/- 80 ng/mL at 22 minutes after arrest. These data suggest that standard dosing of epinephrine through the endotracheal tube during arrest does not produce significant increases in plasma catecholamines or blood pressure. Epinephrine 0.1 mg/kg produces a significant increase in plasma epinephrine levels, but it is not sufficient to produce a significant change in blood pressure.

Detrimental effects of beta-adrenergic stimulation on beta-adrenoceptors and microtubules in the heart

Increased plasma catecholamines - in particular, excessive beta-adrenoceptor activation in chronic heart failure - may easily desensitize the beta-adrenoceptors as well as the postreceptor signal transductions. Since these detrimental changes in the failing heart could be reversible, administration of low-dose beta-blocker, which minimizes the negative inotropic effects, may be effective in attenuating the harmful effects of sympathetic nerve activation. Beta-adrenoceptor stimulation may also produce microtubule disruptions of the cell either through direct action or through an increase in heart rate. Treatment with beta-blockers could attenuate Ca overload by slowing the heart rate and may be useful as a protection from the structural disintegration of the cell. Thus, to clarify the underlying mechanisms of beta-blocker therapy for chronic heart failure, we have to consider not only to the functional aspects but also to the structural changes of the cells.

Effects of buspirone and chlordiazepoxide on plasma catecholamine and corticosterone levels in stressed and nonstressed rats

The effects of intragastric administration of the prototypical benzodiazepine (BDZ) anxiolytic drug chlordiazepoxide (CDP) and the non-BDZ anxiolytic agent buspirone (BUSP) on basal and stress-elevated plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) contents were investigated. Acute dosing of CDP (1–27 mg/kg) produced dose-related increases in basal CS secretion but was without effect on basal NA levels. The high dose of CDP caused a slight short-term A increase. Dose-dependent increases in plasma A, NA and CS contents were observed after acute treatment with BUSP (2 and 20 mg/kg). A medium dose of CDP (9 mg/kg) attenuated the stress-induced CS and A elevations. High doses of CDP that elevated basal CS release prevented a further increase of CS by stress and inhibited the NA and A response to stress. BUSP (2 and 20 mg/kg) was not effective in decreasing the stress-elicited rise of CS, NA or A. Conversely, the 20 mg/kg dose of BUSP enhanced the stress-induced A response. Repeated administration of CDP (9 mg/kg/day for six days) produced tolerance to the elevation of basal CS triggered by acute CDP treatment, but increased the efficacy of the drug's CS and A attenuating action in stressed rats. Repeated administration of BUSP (2 mg/kg/day for six days) also produced tolerance to the acute BUSP-induced effect on basal CS release, but did not affect the stress-induced CS, NA and A responses. It is concluded that the clinically effective anxiolytic BUSP does not have the BDZ-like property to inhibit stress-induced elevations in CS, NA and A. Furthermore, the present data support other evidence that activation of 5-HT 1A receptor mechanisms increases plasma catecholamine and corticosterone concentrations.