Plasma epinephrine in chronically adrenodemedullated rats: lack of response to acute or chronic exercise.

Even if it is well established that epinephrine is a hormone originating from the adrenal medullae, the reappearance of circulating epinephrine has been reported in rats a few days after adrenodemedullation. To verify if the extra-adrenal tissue responsible for this epinephrine production can be stimulated, sham-operated or adrenodemedullated rats, either trained or kept sedentary, were submitted to an acute exercise stimulation test. Blood sampling was done before and after the test in precannulated rats for the determination of plasma epinephrine, norepinephrine, and corticosterone levels. Basal epinephrine levels were significantly reduced in trained and sedentary adrenodemedullated rats compared with their sham-operated counterparts. In response to exercise, there was no significant rise in epinephrine levels in both groups of adrenodemedullated rats. The norepinephrine levels in the basal state and in response to exercise were not altered by adrenodemedullation nor by physical conditioning. Basal corticosterone levels were similar between adrenodemedullated and sham-operated animals, either trained or kept sedentary. In response to exercise, corticosterone levels increased significantly in each group of rats but to a lesser extent in both groups of adrenodemedullated animals. These data indicate that the extra-adrenal epinephrine secretion that develops in the absence of adrenal medullae is not influenced by acute exercise nor by physical training.     

Effect of liver glycogen content on glucose production in running rats

The influence of supranormal compared with normal hepatic glycogen levels on hepatic glucose production (Ra) during exercise was investigated in chronically catheterized rats. Supranormal hepatic glycogen levels were obtained by a 24-h fast-24-h refeeding regimen. During treadmill running for 35 min at a speed of 21 m/min, Ra and plasma glucose increased more (P less than 0.05) and liver glucogen breakdown was larger in fasted-refed compared with control rats, although the stimuli for Ra were higher in control rats, the plasma concentrations of insulin and glucose being lower (P less than 0.05) in control compared with fasted-refed rats. Also, plasma concentrations of glucagon and both catecholamines tended to be higher and muscle glycogenolysis lower in control compared with fasted-refed rats. Lipid metabolism was similar in the two groups. The results indicate that hepatic glycogenolysis during exercise is directly related to hepatic glycogen content. The smaller endocrine glycogenolytic signal in face of higher plasma glucose concentrations in fasted-refed compared with control rats is indicative of metabolic feedback control of glucose mobilization during exercise. However, the higher exercise-induced increase in Ra, plasma glucose, and liver glycogen breakdown in fasted-refed compared with control rats indicates that metabolic feedback mechanisms are not able to accurately match Ra to the metabolic needs of working muscles.     

Muscle and liver glycogen, protein, and triglyceride in the rat. Effect of exercise and of the sympatho-adrenal system

We have previously found that during exercise net muscle glycogen breakdown is impaired in adrenodemedullated rats, as compared with controls. The present study was carried out to elucidate whether, in rats with deficiencies of the sympatho-adrenal system, diminished exercise-induced glycogenolysis in skeletal muscle was accompanied by increased breakdown of triglyceride and/or protein. Thus, the effect of exhausting swimming and of running on concentrations of glycogen, protein, and triglyceride in skeletal muscle and liver were studied in rats with and without deficiencies of the sympatho-adrenal system. In control rats, both swimming and running decreased the concentration of glycogen in fast-twitch red and slow-twitch red muscle whereas concentrations of protein and triglyceride did not decrease. In the liver, swimming depleted glycogen stores but protein and triglyceride concentrations did not decrease. In exercising rats, muscle glycogen breakdown was impaired by adrenodemedullation and restored by infusion of epinephrine. However, impaired glycogen breakdown during exercise was not accompanied by a significant net breakdown of protein or triglyceride. Surgical sympathectomy of the muscles did not influence muscle substrate concentrations. The results indicate that when glycogenolysis in exercising muscle is impeded by adrenodemedullation no compensatory increase in breakdown of triglyceride and protein in muscle or liver takes place. Thus, indirect evidence suggests that, in exercising adrenodemedullated rats, fatty acids from adipose tissue were burnt instead of muscle glycogen.     

Effect of beta-adrenergic blockade on lactate turnover in exercising dogs

Dogs with indwelling catheters in the jugular vein and in the carotid artery ran on the treadmill (slope: 15%, speed: 133 m/min). Lactate turnover and glucose turnover were measured using [U-14C]lactate and [3-3H]glucose as tracers, according to the primed constant-rate infusion method. In addition, the participation of plasma glucose in lactate production (Ra-L) was measured with [U-14C]glucose. Propranolol was given either (A) before exercise (250 micrograms/kg, iv) or (B) in form of a primed infusion administered to the dog running at a steady rate. Measurements of plasma propranolol concentration showed that in type A experiments plasma propranolol fell in 45 min below the lower limit of the complete beta-blockade. In the first 15 min of work Ra-L rose rapidly; then it fell below that of the control (exercise) values. During steady exercise, the elevated Ra-L was decreased by propranolol infusion close to resting values. beta-Blockade doubled the response of glucose production, utilization, and metabolic clearance rate to exercise. In exercising dogs approximately 40-50% of Ra-L arises from plasma glucose. This value was increased by the blockade to 85-90%. It is concluded that glycogenolysis in the working muscle has a dual control: 1) an intracellular control operating at the beginning of exercise, and 2) a hormonal control involving epinephrine and the beta-adrenergic receptors.     

Carbohydrate metabolism in fructose-fed and food-restricted running rats

In chronically catheterized rats hepatic glycogen was increased by fructose (approximately 10 g/kg) gavage (FF rats) or lowered by overnight food restriction (FR rats). [3-3H]- and [U-14C]glucose were infused before, during, and after treadmill running. During exercise the increase in glucose production (Ra) was always directly related to work intensity and faster than the increase in glucose disappearance, resulting in increased plasma glucose levels. At identical work-loads the increase in Ra and plasma glucose as well as liver glycogen breakdown were higher in FF and control (C) rats than in FR rats. Breakdown of muscle glycogen was less in FF than in C rats. Incorporation of [14C]glucose in glycogen at rest and mobilization of label during exercise partly explained that 14C estimates of carbohydrate metabolism disagreed with chemical measurements. In some muscles glycogen depletion was not accompanied by loss of 14C and 3H, indicating futile cycling of glucose. In FR rats a postexercise increase in liver glycogen was seen with 14C/3H similar to that of plasma glucose, indicating direct synthesis from glucose. In conclusion, in exercising rats the increase in glucose production is subjected to feedforward regulation and depends on the liver glycogen concentration. Endogenous glucose may be incorporated in glycogen in working muscle and may be used directly for liver glycogen synthesis rather than after conversion to trioses. Fructose ingestion may diminish muscular glycogen breakdown. The [14C]glucose infusion technique for determination of muscular glycogenolysis is of doubtful value in rats.     

Epinephrine is unessential for stimulation of liver glycogenolysis during exercise

To determine the role of adrenal medullary hormones in controlling the rate of liver glycogenolysis during exercise, adrenodemedullated (ADM) and sham-operated (SO) rats were run on a rodent treadmill at 21 m/min up a 15% grade for 0, 30, or 60 min. Rats were anesthetized by intravenous injection of pentobarbital sodium, and liver, muscle, and blood were collected and frozen. Liver glycogen decreased at similar rates in ADM and SO rats. Hepatic adenosine 3',5'-cyclic monophosphate (cAMP), plasma glucagon, and plasma free fatty acids increased to the same extent in both ADM and SO rats. The adrenodemedullation caused a reduction in glycogenolysis in the fast-twitch white region of the quadriceps, soleus, and lateral gastrocnemius during exercise. The normal exercise-induced increase in blood glucose and lactate and the decline in plasma insulin were not observed in the demedullated rats. During submaximal exercise the principal targets for epinephrine released from the adrenal medulla appear to be pancreatic beta-cells and skeletal muscle and not the liver.     

Epinephrine, glucose, and lactate infusion in exercising adrenodemedullated rats

The purpose of this study was to determine the metabolic function of the marked increase in plasma epinephrine which occurs in fasted rats during treadmill exercise. Fasted adrenodemedullated (ADM) and sham-operated (SHAM) rats were run on a rodent treadmill (21 m/min, 15% grade) for 30 min or until exhaustion. ADM rats were infused with saline, epinephrine, glucose, or lactate during the exercise bouts. ADM saline-infused rats showed markedly reduced endurance, hypoglycemia, elevated plasma insulin, reduced blood lactate, and reduced muscle glycogenolysis compared with exercising SHAM's. Epinephrine infusion corrected all deficiencies. Glucose infusion restored endurance run times and blood glucose to normal without correcting the deficiencies in blood lactate and muscle glycogenolysis. Infusion of lactate partially corrected the hypoglycemia at 30 min of exercise, but endurance was not restored to normal and rats were hypoglycemic at exhaustion. We conclude that in the fasted exercising rat, actions of epinephrine in addition to provision of gluconeogenic substrate are essential for preventing hypoglycemia and allowing the rat to run for long periods of time.     

Effects of glucose infusion in exercising rats

To determine whether feedforward control of liver glycogenolysis during exercise is subject to negative feedback by elevated blood glucose, glucose was infused into exercising rats at a rate that elevated blood glucose greater than 10 mM. Liver glycogen content decreased 22.4 mg/g in saline-infused rats compared with 13.6 mg/g in glucose-infused rats during the first 40 min of treadmill running (21 m/min, 15% grade). Liver adenosine 3',5'-cyclic monophosphate (cAMP) concentration was significantly lower in the glucose-infused rats during the exercise bout. The concentration of hepatic fructose 2,6-bisphosphate remained elevated throughout the exercise bout in glucose-infused rats but decreased markedly in saline-infused rats. Plasma insulin concentration was higher and plasma glucagon concentration lower in glucose-infused rats than in saline-infused rats during exercise. Early in exercise, liver glycogenolysis proceeds in the glucose-infused rats despite the fact that glucose and insulin concentrations are markedly elevated and liver cAMP is unchanged from resting values. These observations suggest the existence of a cAMP-independent feedforward system for activation of liver glycogenolysis that can override classical negative feedback mechanisms during exercise.     

Effects of long-term feeding of high-protein or high-fat diets on the response to exercise in the rat

The aim of this work was to find by which mechanisms an increased availability of plasma free fatty acids (FFA) reduced carbohydrate utilization during exercise. Rats were fed high-protein medium-chain triglycerides (MCT), high-protein long-chain triglycerides (LCT), carbohydrate (CHO) or high-protein low-fat (HP) diets for 5 weeks, and liver and muscle glycogen, gluconeogenesis and FFA oxidation were studied in rested and trained runner rats. In the rested state the hepatic glycogen store was decreased by fat and protein feeding, whereas soleus muscle glycogen concentration was only affected by high-protein diets. The percentage decrease in liver and muscle glycogen stores, after running, was similar in fat-fed, high-protein and CHO-fed rats. The fact that plasma glucose did not drastically change during exercise could be explained by a stimulation of hepatic gluconeogenesis: the activity of phosphoenolpyruvate carboxykinase (PEPCK) and liver phosphoenolpyruvate (PEP) concentration increased as well as cyclic adenosine monophosphate (AMPc) while liver fructose 2,6-bisphosphate decreased and plasma FFA rose. In contrast, the stimulation of gluconeogenesis in rested HP-, MCT- and LCT-fed rats appears to be independent of cyclic AMP.     

Prolactin Release during Exercise in Normal and Adrenodemedullated Untrained Rats Submitted to Central Cholinergic Blockade with Atropine

To study the role of the central cholinergic system in pituitary prolactin (PRL) release during exercise we injected atropine (5 x 10(-7) mol) into the lateral cerebral ventricle of intact or adrenodemedullated (ADM) untrained rats, at rest or submitted to exercise on a treadmill (18 m x min(-1), 5% grade) until exhaustion. The rats were implanted with chronic jugular catheters for blood sampling and with unilateral intracerebroventricular (icv) cannulas placed in the right lateral ventricle. Blood prolactin concentrations were measured before and every 10 min after the start of exercise for a period of 60 min. After the animals started running, plasma prolactin levels rose rapidly in both normal and ADM rats, reaching near maximum at 10 min. Close to exhaustion (19.8 +/- 2.9 min for intact rats and 23.5 +/- 4.1 min for ADM) they were still high, remained increased until 30 min, and returned to preexercise levels at 40 min. Icv injections of atropine decreased the time to exhaustion by 67% in intact rats and by 96.2% in ADM and also reduced the exercise-induced PRL release in both intact (50%) and ADM rats (90%). The results showed that prolactin release induced by exercise was dependent on the exercise workload and could be observed as early as after 10 min of running, remaining increased until 30 min. These data indicate that adrenodemedullation does not affect prolactin secretion induced by exercise, although adrenodemedullated rats proved to be more sensitive to the reducing effect of central cholinergic blockade on their maximal capacity for exercise.     

Endurance vs. strength training: comparison of cardiac structures using normal predicted values

The importance of metabolic feedback regulation vs. feedforward regulation of hepatic glucose production (HGP) during exercise was investigated in rats by infusing glucose intravenously from the onset of running. Glucose infusion equaled the average exercise-induced increase from basal to steady state in HGP found in saline-infused control rats. Rats were studied at two work loads, running at 21 (series I) or 18 m/min (series II) for 35 min. Glucose turnover was measured by means of an intravenous [3H]glucose infusion. HGP was suppressed by glucose infusion corresponding to the infused amount of glucose in both series, except for late in exercise in series I, where HGP plus infused glucose tended to exceed HGP in saline-infused rats (P less than 0.10). Muscle glycogenolysis and fat metabolism were similar in both groups in the two series. Plasma glucose was never elevated, whereas insulin was, in glucose- vs. saline-infused rats of both series. Plasma catecholamines were lower in glucose- compared with saline-infused rats in series II. In conclusion, HGP is very sensitive to metabolic feedback inhibition at low exercise intensities. Feedforward control of HGP may play a role at higher work loads (series I). Exogenously supplied glucose, in moderate amounts, may replace HGP specifically without concomitant changes in mobilization of other substrates.     

Hepatic alpha- and beta-adrenergic receptors are not essential for the increase in R(a) during exercise in diabetes

The purpose of this study was to determine the role of direct hepatic adrenergic stimulation in the control of endogenous glucose production (R(a)) during moderate exercise in poorly controlled alloxan-diabetic dogs. Chronically catheterized and instrumented (flow probes on hepatic artery and portal vein) dogs were made diabetic by administration of alloxan. Each study consisted of a 120-min equilibration, 30-min basal, 150-min moderate exercise, 30-min recovery, and 30-min blockade test period. Either vehicle (control; n = 6) or alpha (phentolamine)- and beta (propranolol)-adrenergic blockers (HAB; n = 6) were infused in the portal vein. In both groups, epinephrine (Epi) and norepinephrine (NE) were infused in the portal vein during the blockade test period to create suprapharmacological levels at the liver. Isotopic ([3-(3)H]glucose, [U-(14)C]alanine) and arteriovenous difference methods were used to assess hepatic function. Arterial plasma glucose was similar in controls (345 +/- 24 mg/dl) and HAB (336 +/- 23 mg/dl) and was unchanged by exercise. Basal arterial insulin was 5 +/- 1 mU/ml in controls and 4 +/- 1 mU/ml in HAB and fell by approximately 50% during exercise in both groups. Basal arterial glucagon was similar in controls (56 +/- 10 pg/ml) and HAB (55 +/- 7 pg/ml) and rose similarly, by approximately 1.4-fold, with exercise in both groups. Despite greater arterial Epi and NE levels in HAB compared with controls during the basal and exercise periods, exercise-induced increases in catecholamines from basal were similar in both groups. Gluconeogenic conversion from alanine and lactate and the intrahepatic efficiency of this process were increased by twofold during exercise in both groups. R(a) rose similarly by 2.9 +/- 0.7 and 2.7 +/- 1.0 mg. kg(-1). min(-1) at time = 150 min during exercise in controls and HAB. During the blockade test period, arterial plasma glucose and R(a) rose to 454 +/- 43 mg/dl and 11.3 mg. kg(-1). min(-1) in controls, respectively, but were essentially unchanged in HAB. The attenuated response to the blockade test in HAB substantiates the effectiveness of the hepatic adrenergic blockade. In conclusion, these results demonstrate that direct hepatic adrenergic stimulation does not play a role in the stimulation of R(a) during exercise in poorly controlled diabetes.     

Effect of adrenal denervation on the glucose, insulin, and glucagon responses to exercise in sheep

Previous studies suggest that adrenal catecholamines mediate, in part, the glucose and pancreatic hormonal responses to exercise in sheep. This was examined in sheep whose adrenals were denervated to prevent stress-induced changes in catecholamine secretion. The innervation to the right adrenal gland was severed and the left adrenal was removed. Adrenal denervation was associated with a reduction in exercise-induced hyperglycemia and impairment, as measured by [2-3H]glucose, of the increase in glucose appearance during the first 10 min of exercise and increased metabolic clearance rate of glucose after 20 min of exercise. Insulin concentrations were significantly higher during exercise after adrenal denervation than in the controls. Adrenal denervation did not alter the rise in glucagon due to exercise. These effects are consistent with adrenomedullary hormonal stimulation of hepatic and muscular glycogenolysis, either directly or indirectly through the regulation of insulin secretion during exercise in sheep.     

Exercise endurance and fuel utilization: a reevaluation of the effects of fasting

The effect of fasting on energy utilization during running or swimming was studied in adult male Wistar rats. Compared with fed rats, fasted animals displayed a decreased contribution of carbohydrates in energy supply, with decreased liver and muscle glycogen contents and decreased rate of glycogen breakdown. This was compensated by an enhanced rate of beta-oxidation. In addition, fasting induced an exaggerated sympathoadrenal response during exercise, reflected by a greater epinephrine plasma level and a higher norepinephrine turnover rate in both liver and soleus. Nevertheless, endurance capacity was similar in fasted and fed animals. These results contrast with the impairment of endurance observed in fasting humans but also with the improvement of endurance in rats previously reported by Dohm et al. (J. Appl. Physiol. 55: 830-833, 1983). These data suggest that the metabolic responses to exercise subsequent to food deprivation depend not only on the considered species but also, in the same species (rat), on the age of the animals and the duration of the fast. These factors probably determine the hormonal secretion and substrate utilization during prolonged exercise in fasting conditions.     

Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart

Heart sympathetic denervation can accompany Parkinson's disease, but the effect of this denervation on cardiac lipid-mediated signaling is unknown. To address this issue, rats were sympathetically denervated with 6-hydroxydopamine (6-OHDA, 50 mg/kg ip) and infused with 170 muCi/kg of either [1-(14)C]palmitic acid ([1-(14)C]16:0) or [1-(14)C]arachidonic acid ([1-(14)C]20:4 n-6), and kinetic parameters were assessed using a steady-state radiotracer model. Heart norepinephrine and epinephrine levels were decreased 82 and 85%, respectively, in denervated rats, and this correlated with a 34% reduction in weight gain in treated rats. Fatty acid tracer uptake was not significantly different between groups for either tracer, although the dilution coefficient lambda was increased in [1-(14)C]20:4 n-6-infused rats, which indicates that less 20:4 n-6 was recycled in denervated rats. In [1-(14)C]16:0-infused rats, incorporation rate and turnover values of 16:0 in stable lipid compartments were unchanged, which is indicative of preservation of beta-oxidation. In [1-(14)C]20:4 n-6-infused rats, there were dramatic reductions in incorporation rate (60-84%) and turnover value (56-85%) in denervated rats that were dependent upon the lipid compartment. In addition, phospholipase A(2) activity was reduced 40% in treated rats, which is consistent with the reduction observed in 20:4 n-6 turnover. These results demonstrate marked reductions in 20:4 n-6 incorporation rate and turnover in sympathetic denervated rats and thereby suggest an effect on lipid-mediated signal transduction mediated by a reduction in phospholipase A(2) activity.     

Accelerated turnover of blood glucose in pertussis-sensitized rats due to combined actions of endogenous insulin and adrenergic beta-stimulation.

1. Epinephrine-induced hyperglycemia was attenuated by the treatment of rats with pertussis vaccine, but this attenuation was abolished when endogenous insulin was suppressed by streptozotocin or anti-insulin serum. It was concluded that epinephrine-induced hyperglycemia was counterbalanced by the hypoglycemic action of insulin, the secretion of which was markedly potentiated in pertussis-sensitized rats. 2. Without epinephrine, no hypoglycemia developed in pertussis-sensitized rats despite the higher blood level of insulin. Tracer experiments with [14C,3H] glucose or [14C]bicarbaonate showed that, in pertussis-sensitized rats, more glucose was liberated into the blood from hepatic gluconeogenesis at the expense of hepatic glycogenesis, thereby accelerating the turnover of blood glucose. 3. Since this activation of hepatic glucose production was reduced by propranolol, a beta-adrenergic blocking agent, it is very likely that adrenergic beta-stimulation is, at least partly, responsible for the metabolic alterations observed in pertussis-sensitized rats.     

Diminished hormonal responses to exercise in trained rats

Male rats (120 g) either were subjected to a 12-wk physical training program (T rats) or were sedentary controls (C rats). Subsequently the rats were killed at rest or after a 45- or 90-min forced swim. At rest, T rats had higher liver and muscle glycogen concentrations but lower plasma insulin. During exercise, blood glucose increased 60% in T rats but decreased 20% in C rats. Plasma glucagon and insulin concentrations did not change in T rats but plasma glucagon increased and insulin decreased markedly in C rats. Plasma epinephrine (90 min: range, 0.78-2.96 ng-ml-1, (T) vs. 4.42-15.67 (C)) and norepinephrine (90 min: 0.70-2.22 (T) vs. 2.50-6.10 (C)) were lower in T than in C rats. Hepatic glycogen decreased substantially and, as with muscle glycogen, the decrease was parallel in T and C rats. The plasma concentrations of free fatty acids were higher but lactate and alanine lower in T than in C rats. In trained rats the hormonal response to exercise is blunted partly due to higher glucose concentrations. In these rats adipose tissue sensitivity to catecholamines is increased, and changes in glucagon and insulin concentrations are not necessary for increased lipolysis and hepatic glycogen depletion during exercise.     

Carbohydrate metabolism during and after exercise in rats: studies with radioglucose

Carbohydrate metabolism in exercise, including regulation of glucose production, was studied by isotope-dilution methods, and these were evaluated. Chronically catheterized rats were examined before, during, and after 45 min of running at either low (LIE) or moderate (MIE) intensity. Glucose production (Ra) and disappearance (Rd), as well as muscular glycogen breakdown (Gly), were estimated by primed constant infusions of [3-3H]- and [U-14 C]glucose, and pyruvate oxidation was estimated by sampling of expired 14CO2. During exercise, Ra increased faster than Rd and was, as were steady-state glucose concentration (G) and Gly, directly related to exercise intensity. During recovery Ra and G decreased rapidly, but after MIE, G showed a rebound increase. 14C estimates and chemical measurements sometimes disagreed. Methodological evaluation showed marked incorporation of label in glycogen, lipid, and protein at rest and mobilization of label during exercise. 14CO2 recovery in expired air ranged from only 50% at rest to 77% during MIE. In conclusion, during exercise, mobilization of hepatic glycogen is a primary event and not secondary to increased muscular demand. During and after exercise, plasma glycogen is not precisely controlled at euglycemic levels. Isotope methods may be used to study carbohydrate metabolism in exercising rats, but the results (especially 14C data) should be interpreted with caution.     

Action of hepatic chalones on the proliferation of hepatocytes from intact and denervated livers

The paper is concerned with the action of chalones, tissue-specific inhibitors of cell proliferation, on DNA synthesis and mitotic activity of hepatocytes in the intact and denervated liver during regeneration. Experiments were made on Wistar rats. Liver denervation was performed by bilateral subdiaphragmal vagotomy. In control and vagotomized animals, two thirds of the liver was resected. The data obtained indicate that chalones noticeably reduce the number of DNA-synthesizing cells and mitoses in the regenerating liver of intact animals. During regeneration of the denervated liver, chalones do not produce any inhibitory action on the intensity of proliferation. Analysis of the data obtained allows a conclusion that preservation of adequate innervation of the organ is needed for realization of the action of hepatic chalones.     

Effects of exercise on plasma catecholamine levels in the toad, Bufo paracnemis: role of the adrenals and neural control

Resting plasma epinephrine (E) and norepinephrine (N) concentrations for intact toads (Bufo paracnemis) were 5.57+/-1.0 and 0.88+/-0.38 ng/ml, respectively. Exercise induced a significant increase in heart rate, blood pressure and plasma epinephrine (about 4.3 times), whereas norepinephrine remained unchanged. The resting [E]/[N] ratio was 6.3 and increased to 32.9 during exercise. Adrenal denervation did not alter the basal plasma catecholamine or norepinephrine levels after exercise, but prevented the increase in epinephrine during exercise, suggesting that in the intact toad this increase is due to adrenal secretion whereas resting norepinephrine may be liberated by extra-adrenal chromaffin tissues. This also suggests that the adrenal glands can release selectively the two catecholamines. The increases in heart rate and blood pressure in denervated toads were not significantly different from those of intact animals, suggesting that during exercise the sympathetic nerves play the main role in inducing cardiovascular responses. Spinal transection induced a significant increase in basal norepinephrine levels, which remained elevated after exercise. Since spinal toads are unable to perform spontaneous movements it is possible that this increase may be caused by this stressful condition. The increases in heart rate and blood pressure observed in spinal toads during exercise may be due to direct mechanical effects of venous return on the heart.