Increased Plasma Catecholamine Levels Research Articles

Effect of bretylium tosylate on ventricular fibrillation threshold during hypothermia in dogs

How bretylium tosylate affected the ventricular fibrillation threshold, electrophysiological parameters, and plasma catecholamine levels during hypothermia in dogs was studied. Threshold for ventricular fibrillation was determined by programmed electrical stimulation using a stimulation protocol that involved applying a maximum of five extrastimuli at body temperatures 37, 34, 31, 28, and 25°C, and at the same temperatures during rewarming. Electrocardiogram, epicardial monophasic action potentials (MAP), and electrograms were recorded, and ventricular effective refractory period (VERP) was determined at each of the above temperatures. In one group (n = 7), a bolus dosage of bretylium tosylate (BT), 6 mg/kg body wt, was administered at 25°C before rewarming. Another group (n = 4) was exposed to cooling and rewarming without addition of BT. Cooling to 25°C reduced ventricular fibrillation threshold linearly, reduced heart rate, increased VERP and MAP, and slowed myocardial conduction velocity in both groups. There was no overall increase in plasma catecholamine levels during cooling. Addition of BT at 25°C increased ventricular fibrillation threshold during rewarming compared with cooling. Addition of BT at 25°C increased VERP by ±32 milliseconds and the corrected JT time by 0.06 ± 0.02 seconds. VERP and JT c increased during rewarming with BT compared with cooling with no drug. BT had no effect on conduction velocity, and plasma catecholamine levels were not reduced. The antiarrhythmic effect of BT during hypothermia was attributed to an increased wavelength of refractoriness by its increase in the refractory period. This increased wavelength of refractoriness may prevent excitable gaps or increase circuit pathway in the setting of reentry arrhythmias.

Acute cardiotoxic effects of cocaine and a hyperadrenergic state in anesthetized dogs

The purpose of this study was to determine whether a subthreshold dose of cocaine (one that is well-tolerated in a resting state with no significant hemodynamic changes) causes cardiotoxic responses when superimposed upon a subthreshold infusion of norepinephrine. Adult mongrel dogs were anesthetized, instrumented and assigned to one of five treatment groups: saline control, norepinephrine infusion (0.75 μg/kg/min, i.v. for 60 min); cocaine (5.0 mg/kg, i.v. bolus); combination of cocaine (0.5 mg/kg) or (5.0 mg/kg) with the last 45 min of norepinephrine infusion. The combination groups exhibited increased blood pressure and contracility ( dP d t ), and a greater variety and frequency of arrhythmias. Cocaine did not increase plasma catecholamine levels beyond norepinephrine alone. There were significantly more contraction band lesions/mm 2 with cocaine in combination with norepinephrine than in any of the individual treatment groups. These data indicate that, even in anesthetized animals, a well-tolerated dose of cocaine may become toxic when superimposed on an excited or hyperadrenergic state with elevated levels of norepinephrine.

Blood pressure normalization in carotid barodenervated rats: role of cardiac output.

This study evaluated the role of sympathetic nervous system (SNS) activity, peripheral hemodynamic changes, and pressure diuresis in blood pressure (BP) normalization in carotid barodenervated rats. The acute and short-term effects of carotid barodenervation or sham operation on blood pressure, heart rate, cardiac output, stroke volume, total peripheral resistance, and plasma catecholamine levels were determined. Changes in plasma volume, urine output, and water and food intakes were also measured. Surgical denervation of the carotid baroreceptors resulted in rapid rises in blood pressure and heart rate in anesthetized rats. These changes were associated with significant increases in plasma catecholamine levels and total peripheral resistance whereas the cardiac index and stroke volume remained unchanged. After recovery from the anesthesia, the blood pressure of carotid barodenervated rats was still significantly higher than that of sham-operated rats at 3 and 24 h after denervation and returned to sham-operated levels by 48 h. Plasma catecholamine levels and total peripheral resistance were higher in carotid barodenervated than in sham-operated rats on the 2 days following surgery. On the other hand, cardiac index (32 +/- 1 vs. 40 +/- 2 mL.min-1 x 100 g-1 body mass) and stroke volume (205 +/- 13 vs. 283 +/- 4 microL/beat) were significantly lower on day 2 in carotid barodenervated than in sham-operated rats, which suggests a compensatory role for carotid output in blood pressure normalization after carotid barodenervation. Both carotid barodenervation and sham operation caused a reduction in water and food intakes but the responses were greater in carotid barodenervated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

THE EFFECTS OF ACCLIMATION TEMPERATURE ON THE DYNAMICS OF CATECHOLAMINE RELEASE DURING ACUTE HYPOXIA IN THE RAINBOW TROUT ONCORHYNCHUS MYKISS

The response of cannulated rainbow trout (Oncorhynchus mykiss) to acute hypoxia was studied in fish acclimated to two temperatures (5 and 15 °C). Blood/water respiratory variables and plasma catecholamine levels were measured before and 15 min after exposure to hypoxic water varying between 4.0 and 10.7 kPa (30­80 mmHg) oxygen partial pressure (PwO2). Arterial blood PO2 (PaO2) and oxygen content (CaO2) fell during hypoxia in a similar manner at both temperatures, although the changes in CaO2 were often more pronounced in the fish acclimated to 15 °C. Regardless of acclimation temperature, plasma catecholamine levels were consistently elevated at PwO2 values below 8.0 kPa (60 mmHg); the largest increases in plasma catecholamine levels occurred below PwO2=5.3 kPa (40 mmHg). Adrenaline was the predominant catecholamine released into the circulation. Adrenaline was released at PwO2 values of 8.0 kPa or below, whereas noradrenaline was released at PwO2 values of 6.7 kPa or below. The construction of in vivo oxygen dissociation curves demonstrated an obvious effect of acclimation temperature on haemoglobin (Hb) oxygen-affinity; the P50 values at 15 °C and 5 °C were 3.6 kPa (26.7 mmHg) and 1.9 kPa (14.0 mmHg), respectively. At 15 °C, catecholamines were released into the circulation abruptly at a PaO2 threshold of 4.6 kPa (34.5 mmHg) while at 5 °C the catecholamine release threshold was lowered to 3.3 kPa (24.5 mmHg). The difference in the PaO2 catecholamine release thresholds was roughly equivalent to the difference in the P50 values at the two distinct temperatures. Catecholamine release thresholds, calculated on the basis of arterial blood oxygen-saturation (expressed as CaO2/[Hb]), were similar at both temperatures and were approximately equal to 53­55 % Hb O2-saturation. The results support the contention that the lowering of blood oxygen content/saturation rather than PO2 per se is the proximate stimulus/signal causing catecholamine release in rainbow trout during acute hypoxia.

Roles of catecholamines and corticosterone during anoxia and recovery at 5 degrees C in turtles.

The roles of the catecholamines and corticosterone in glucose regulation during 28 days of submergence anoxia and air-breathing recovery at 5 degrees C in the turtle Chrysemys picta were examined. Anoxia resulted in an increase in mean plasma epinephrine and norepinephrine levels (from 42 and 49 to 966 and 3,826 pg/ml, respectively) and a decrease in hepatic glycogen levels. Despite the increase in plasma catecholamine levels, plasma glucose levels did not change, and the percent of the alpha form of hepatic glycogen phosphorylase was decreased compared with normoxic controls. Plasma levels of lactate increased from 1.5 to 95 mM, and corticosterone decreased during anoxia. During recovery in air, corticosterone returned to control levels within 1 day, and plasma lactate levels slowly decreased. In contrast to a previous study on anoxic turtles at 22 degrees C, at 5 degrees C the catecholamines do not stimulate hepatic glycogenolysis by increasing the level of glycogen phosphorylase alpha. The results do not support the hypothesis that corticosterone enhances lactate clearance from turtle plasma during recovery from anoxia.

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.

Left ventricular filling and stress response pattern in essential hypertension

purpose: To evaluate whether impaired left ventricular filling determines the hemodynamic responses to isometric and orthostatic stress in a population with mild essential hypertension. patients and methods: The study population consisted of 32 patients with essential hypertension who were subdivided into those with preserved left ventricular filling (15 patients) and those with impaired left ventricular filling (17 patients). Echocardiograms were obtained before hemodynamic assessment was performed. Isometric stress and head-up tilt tests were done with a recovery period of at least 10 minutes between each to allow for blood pressure and heart rate to return to baseline. Hemodynamic reassessment was performed during the last minute of each test and at the end of the recovery period. Plasma epinephrine, norepinephrine, and dopamine levels were determined by radioenzymatic method. results: Isometric stress increased mean arterial pressure by 30% (p <0.0001) by an increase in cardiac output (p <0.0001) and total peripheral resistance (p <0.0001) associated with an increase in plasma catecholamine levels (p <0.0001). Patients with preserved left ventricular filling had an increase in arterial pressure predominantly through an elevation in cardiac output (17%, p <0.0001) associated with a small increase in plasma norepinephrine levels (p <0.05) and in peripheral resistance (11%, p <0.05). In contrast, patients with impaired left ventricular filling had an increase in arterial pressure mainly through an increase in peripheral resistance (25%, p <0.0001) that was associated with a 45% elevation in plasma norepinephrine levels (p <0.0001). Orthostatic stress (passive head-up tilt) caused an exaggerated decrease in stroke volume (p <0.01) and cardiac output (p <0.01) in patients with impaired left ventricular filling when compared with those with preserved diastolic function. conclusion: Impaired left ventricular filling blunts the response of the heart to isometric and orthostatic stress. As a consequence, hypertensive patients with impaired ventricular filling respond to these stressors with enhanced sympathetic stimulation and exaggerated vasoconstriction.

The Role of Circulating Catecholamines in the Ventilatory and Hypertensive Responses to Hypoxia in the Atlantic Cod (Gadus morhua)

This is the first description of the ventilatory response of the Atlantic cod (Gadus morhua) to hypoxia. Using a pharmacological approach, we tested the hypotheses that during hypoxia (1) elevation of circulating catecholamines, arising from chromaffin tissue or peripheral adrenergic neurones, contributes to hyperventilation and that (2) the hyperventilatory response can be modulated by the hypoxia-induced hypertension. The ventilatory response to hypoxia (final water PO₂ = 46 mmHg, reached in ≤25 min) was not significantly altered by pretreatment offish with either α-or β-adrenoceptor antagonists (phentolamine or sotalol, respectively) or with an inhibitor of catecholamine release from peripheral neurones (bretylium), despite a significant increase in plasma catecholamine levels in all treatment groups. Since the utilized regime did not induce metabolic acidosis (a potential ventilatory stimulant), we conclude that the hyperventilation was caused solely by a depression of the oxygen status. Although changes in the internal as well as the external oxygen status may have potentially contributed to the hyperventilation, we suggest, on the basis of the rapid ventilatory response after only small depressions of water PO₂, that the initial stimulus is external. During hypoxia, a doubling of mean ventral aortic blood pressure was observed. This elevation of blood pressure was due to an increased adrenergic nervous and humoral activity. The lack of modification in the ventilatory response to hypoxia after transient or persistent abolishment of the hypertension by pharmacological agents (bretylium or phentolamine, respectively) indicated that during hypoxia there was no relationship between blood pressure and ventilation in this species.

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.

Effect of space flights on plasma hormone levels in man and in experimental animal

An important increase of plasma hormone levels like insulin, TSH and aldosterone was observed in human subjects after space flights, however in the changes of plasma content of ACTH, cortisol, adrenaline and noradrenaline the individual variations were observed in relation to number and duration of space flight. For evaluation of the effects of these changes in plasma hormone levels on metabolic processes also the experiments with small animals subjected to space flights on a board of biosatellite of Cosmos series were running. An elevation of plasma levels of corticosterone, adrenaline, noradrenaline and insulin was found in rats after the space flights of duration from 7 to 20 days. It was demonstrated, that the increase of corticosterone in plasma is followed by the activation of enzymes involved in the aminoacid metabolism in rat liver (tyrosine aminotransferase, tryptophanpyrolase, alanine aminotransferase and aspartate aminotransferase). After a short recovery period (2 to 6 days) the plasma corticosterone concentration and also the activity of liver enzymes returned to control levels. The exposition of animals to stress stimuli during this recovery period showed higher response of corticosterone levels in flight rats as compared to intact controls. The increase of plasma catecholamine levels was not followed by elevation of lipolysis in adipose tissue. This is due to lower response of adipose tissue to catecholamine because a decrease of the stimulation of lipolysis by noradrenaline was observed in animals after space flight. The increase of insulin was not followed by adequate decrease of glucose concentration suggesting a disturbances in glucose utilization similarly as in cosmonauts after a long-term space flight. These results showed that changes in plasma hormone levels, observed after space flight, affected the regulation of metabolic processes in tissues.

Effect of capsaicin‐sensitive sensory nerves on plasma glucose and catecholamine levels during 2‐deoxyglucose‐induced stress in conscious rats

1. Sensory fibres innervate the adrenal medulla but their function is not known. In this paper we have studied the effect of capsaicin-sensitive sensory fibres on the adrenal catecholamine (CA) response and blood glucose response to 2-deoxyglucose (2-DG)-induced glucopenic stress in conscious rats. 2. 2-DG at 500 mg kg-1 (i.v.) induced a 2.5 fold increase in plasma glucose levels, a 3.5 fold increase in inferior vena caval (i.v.c.) plasma noradrenaline (NA) levels and a 7 fold increase in i.v.c. plasma adrenaline (Ad) levels over 60 min. The hyperglyaemia in response to 2-DG was attenuated by pentolinium and by left splanchnicotomy plus right adrenalectomy. These procedures also caused a complete inhibition of the increase in plasma CA. 3. The hyperglycaemia in response to 2-DG was attenuated by pretreatment of rats with capsaicin as neonates, suggesting that capsaicin-sensitive sensory fibres are required for regulation of plasma glucose in response to glucopenic stress. 4. The increase in i.v.c. plasma CA levels in response to 2-DG during the early phase of glucopenia (first 30 min) in the conscious rats pretreated with capsaicin was the same as in the rats pretreated with vehicle alone. During the later phase of glucopenia (after 45 min), the increase in plasma CA levels in rats pretreated with capsaicin was higher than in the rats pretreated with vehicle alone. 5. In vehicle-pretreated rats and capsaicin-pretreated rats the tissue NA and Ad levels in the adrenal medulla after 8 h of stress were depleted to the same extent. However, tissue CA levels in the capsaicin group recovered faster over 24 h than in the vehicle group. 6. These results indicate that capsaicin-sensitive sensory fibres are not required to maintain adrenal CA secretion during glucopenic stress in the conscious rat but are required for maintenance of blood glucose levels.

Catecholamine release controlled by blood oxygen tension during deep hypoxia in trout: effect on red blood cell Na/H exchanger activity

Changes in plasma catecholamine levels were measured in trout exposed to acute hypoxia, in order to correlate with acid-base disturbances due to activation of the cAMP-dependent Na +/H + antiporters of red blood cells, as previously described (Fiévet B., Respir. Physiol. 74, 99–114, 1988). The extracellular acidosis corresponding with the stimulation of the exchangers, occurred when arterial oxygen partial pressure (Pa O 2 ) reached around 15 Torr (Thomas S., Respir. Physiol. 74, 77–90, 1988). This blood pH drop coincide with a marked increase in plasma catecholamine levels. The catecholamine secretion was transient and the hormones were cleared provided Pa O 2 remained above 10 Torr. On the other hand, when Pa O 2 remained below 10 Torr, there was a persistent secretion of catecholamines. This is in agreement with the fact that the exchangers are ‘turned off’ or sustained when Pa O 2 remains above or below 10 Torr respectively, as previously described. Following the transient hormone peak when Pa O 2 stabilized above 10 Torr, it was possible to trigger the second pattern of continuous catecholamine secretion by controlling water P O 2 so that Pa O 2 declined below 10 Torr. We conclude that the blood oxygen level controls catecholamine secretion during deep hypoxia.

Reversal by ethanol of the hypotensive effect of clonidine in conscious spontaneously hypertensive rats.

We studied the acute effect of ethanol on the hypotensive response to clonidine in conscious spontaneously hypertensive rats. When administered during the hypotensive response to clonidine, ethanol not only reversed the response but also caused a slight but significant short-lived pressor effect. The maximal hypotensive effect of graded doses of clonidine was significantly (p less than 0.05) attenuated by a dose of 1 g/kg ethanol, which resulted in a peak blood ethanol concentration of 54.2 +/- 6.3 mg/dl. The data strongly suggest the adverse effect of ethanol on the hypotensive response to clonidine is ethanol mediated and that their antagonistic interaction is both reversible and reproducible because: 1) an equal volume of saline had no effect on the hemodynamic responses to clonidine and 2) crossing over ethanol and saline treatments on days 2 and 3, which allowed longitudinal comparisons, showed that the effect of ethanol was similar both in naive rats (day 1) and in rats that were pre-exposed to ethanol (day 3). Whether this negative effect of ethanol also involves other antihypertensive agents that do not act primarily by a central nervous system mechanism was investigated. The same dose of ethanol had little or no effect on the hypotensive response to hydralazine, suggesting the negative effect of ethanol is selective to centrally acting antihypertensive agents. Although the mechanism by which ethanol reverses the hypotensive effect of clonidine is not known, it is possible that it involves an ethanol-evoked increase in plasma catecholamine levels, which are known to be decreased by clonidine. That ethanol did not reverse the hypotensive effect of hydralazine, which is also known to be associated with increased plasma catecholamine levels, supports this notion. The findings of the present study may explain, at least in part, why regular use of alcohol is associated with an inadequate control of blood pressure in treated hypertensive patients who are regular consumers of alcohol.

Arterial plasma norepinephrine correlates to blood pressure in middle-aged men with sustained essential hypertension

Increased plasma catecholamine levels assessed from the venous blood have been found in a number of studies of younger patients with essential hypertension, but hypertensive-normotensive differences could not easily be demonstrated in subjects above 40 years of age. For several reasons, measurement of arterial plasma catecholamines may be a more sensitive tool for the detection of hypertensive-normotensive differences. The present study therefore aimed at examining both venous and arterial plasma catecholamines in a group of white men, all 50 years of age, with never-treated, established essential hypertension ( n = 61, blood pressure 165 ± 2 112 ± 1 mm Hg , means ± SE) and comparing them with a similar group of normotensive men ( n = 51, blood pressure 128 ± 1 85 ± 1 mm Hg ). Arterial and venous plasma epinephrine, heart rate, and body weight were significantly elevated in the hypertensive group. Plasma norepinephrine was similar between the groups in the venous blood, whereas in the arterial blood the values in hypertensive subjects were moderately, but significantly increased ( p < 0.03). However, stepwise multiple regression analysis suggested arterial plasma norepinephrine was the only significant independent explanatory variable of raised blood pressure in the hypertensive group ( r = 0.51, t = 4.05, p = 0.0002). Such a relationship was not found in the normotensive group. Thus based on measurements in arterial blood, we conclude that plasma norepinephrine, representing sympathetic tone, may be an important pathogenetic factor for high blood pressure in middle-aged men with established hypertension.

Developmental changes in adrenergic regulation of fetal arginine vasopressin secretion.

Fetal adaptation to the extrauterine environment is associated with profound alterations in pulmonary, renal, and cardiovascular functions. Coincident with these changes are a variety of endocrine responses including concomitant increases in plasma catecholamine and arginine vasopressin (AVP) levels. In view of the demonstrated interaction between the sympathoadrenal system and the neurohypophysis in adult mammals, we questioned whether increases in plasma catecholamine levels in the fetus affect fetal plasma AVP levels and whether catecholamine-AVP interactions change developmentally. Chronically catheterized fetal lambs at either 131 +/- 1 (preterm) or 142 +/- 1 days (term) received graded infusions of either epinephrine (E) or norepinephrine (NE) at rates of 0.04, 0.2, 0.75, 1.5, and 3.0 micrograms.min-1.kg-1 during successive 40-min infusion periods. Plasma AVP concentrations in term animals significantly increased (1.4 +/- 0.1 to 5.1 +/- 1.6 pg AVP/ml) in response to E infusion of 0.75 microgram.min-1.kg-1 or greater. The log-linear dose response curves for each animal were used to determine the minimum plasma E concentration required to stimulate AVP secretion or "threshold." The mean plasma E threshold for AVP secretion was significantly lower in term animals (1.4 +/- 0.4 ng/ml) than in preterm animals (6.6 +/- 0.9 ng/ml). Plasma E levels were positively correlated with plasma AVP levels (r = 0.90) above the threshold value in both groups. Changes in plasma AVP levels were observed in preterm or term animals in response to NE only at the highest infusion rate studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating Catecholamines and Swimming Performance in the Atlantic Cod, Gadus Morhua

ABSTRACT Sectioning the first four pairs of spinal nerves prevents the large increase in circulating catecholamine concentrations seen in Atlantic cod swimming at their critical velocity (Ucrit). There is also a significant reduction in the swimming performance of the fish. To test whether this reduced performance results from the lack of increase in plasma catecholamine levels or from the fact that other organs are also denervated by the operative procedure, a mixture of adrenaline and noradrenaline was infused into swimming, denervated fish. This caused a significant increase in their Ucrit-It is concluded, therefore, that the rise in plasma catecholamine levels seen in Atlantic cod swimming at their maximum sustainable velocity enhances the swimming performance of these fish.

Age-related changes of noradrenergic innervation of rat splanchnic blood vessels: a histofluorescence and neurochemical study

The influence of ageing on the noradrenergic innervation of superior mesenteric artery and vein, renal artery and vein, and portal vein was studied in male Wistar rats by means of catecholamine histofluorescence, image analysis techniques and high pressure chromatography with electrochemical detection. Old age was accompanied by a marked increase in the density of noradrenergic innervation and an increase of noradrenaline levels in superior mesenteric artery, renal artery, and portal vein. In contrast, no significant age-related changes were observed in the density of noradrenergic innervation or in noradrenaline levels in superior mesenteric and renal vein. The present data indicate that, at least in superior mesenteric and renal artery and portal vein, senescence is not accompanied by loss or by lack of change in the noradrenergic innervation as commonly believed to be the case in many vascular trees. On the basis of our findings it cannot be excluded that increased plasma catecholamine levels observed in senescence derive, in part, from perivascular sympathetic endings.

The effect of alcohol inhalation on the cardiovascular state of the rat.

Rats were exposed to alcohol vapors by an inhalation technique and blood pressure and its reactivity and platelet aggregation were measured. Acute exposure to alcohol levels which produced moderate blood alcohol concentration (BAC) was associated with increased vascular production of prostacyclin (PGI2) and plasma catecholamines, whereas platelet production of thromboxane (TXA2) decreased. Blood pressure is elevated in these animals, however, the platelet aggregating and pressor effects of noradrenaline (NE) were decreased. Chronic exposure to high BAC is associated with a dramatic reduction in vascular and platelet prostaglandin (PG) production and a marked increase in plasma catecholamine levels. Platelet aggregation decreased in these animals, however, the pressor effect of TXA2 and NE was significantly increased. The fatty acid precursors to PG were reduced by 50% in the lipid extracts of these preparations. These findings suggest that alterations in fatty acid metabolism may lead to a functional deficiency in PG production from dependent rats. Qualitative differences may exist between acute and chronic exposure with respect to the cardiovascular state. Locally produced PG and circulating catecholamines may mediate alcohol-induced alterations in vascular smooth muscle tone and platelet aggregation.

Alterations of beta-adrenoceptors on human leukocyte subsets induced by dynamic exercise: effect of prednisone.

1. In order to investigate exercise-induced changes of beta 2-adrenoceptors on human leukocyte subsets, beta-adrenoceptor density was determined as specific binding of [125I]-iodocyanopindolol to granulocytes, monocytes, B and T lymphocytes of six subjects immediately before and after exercise and after 30 min of rest. 2. A 10 min graded bicycle exercise with a workload of 50-250 W caused a transient increase of granulocytes, monocytes, B and T cells of about 32, 43, 120 and 25%, respectively. 3. While the number of beta 2-adrenoceptors in granulocytes remained unchanged, beta-adrenoceptor densities in B cells, T cells and monocytes increased from pre-exercise mean values of 2730, 870 and 2400 binding sites/cell to 3500, 1230 and 3220 binding sites/cell, respectively, under physical stress. The rise in receptor numbers was accompanied by an enhanced isoprenaline-stimulated cyclic AMP formation in unfractionated mononuclear leukocytes (MNL) of about 26% as well as by a 2-3-fold increase in plasma catecholamine levels. Cell concentrations, beta 2-adrenoceptor numbers and adrenergic responsiveness returned to normal after 30 min rest. 4. Administration of 60 mg prednisone 2 h before exercise resulted in granulocytosis and lymphopenia with a preponderant effect on the exercise-induced rise in B cells and monocytes. Corticosteroids showed no effect on stress-induced changes of beta 2-adrenoceptors and responsiveness. 5. It is concluded that exercise-induced increases in beta 2-adrenoceptor density and adrenergic responsiveness of unfractionated MNL are caused by a release of receptor-enriched cells into the circulation, particularly of B lymphocytes and monocytes which carry the highest beta 2-adrenoceptor density.

The effects of caffeine on various body systems: A review

Caffeine is the most widely consumed drug in Western society. The intake of caffeine-containing beverages in many adults and children often reaches levels that can induce pharmacological effects. Ninety-nine percent of ingested caffeine is absorbed and distributed to all tissues and organs. The effects of caffeine intake differ greatly according to acute or chronic intake, level of intake, and the development of tolerance. Caffeine administered acutely to non-users or recent abstainers can induce hypertension, arrhythmias, altered myocardial function, increased plasma catecholamine levels, plasma renin activity, serum cholesterol levels, increased production of urine, gastric acid secretion, and alterations in mood and sleep patterns. Tolerance to chronic caffeine intake develops in most individuals, with the cessation of its effects on the renal system, the cardiovascular system, the gastrointestinal system and, to some extent, the central nervous system. Moderate caffeine consumers probably need to have little concern for the effect of caffeine intake on their health if their other life-style habits are also moderate.