The influence of fitness on neuroendocrine responses to exhaustive treadmill exercise

Neuroendocrine and sympathoadrenal responses to exhaustive graded treadmill exercise were examined in 17 male subjects of varying degrees of fitness. The mean duration of exercise to exhaustion was 15.2 +/- 0.7 (+/- SE) min. Exercise duration was inversely correlated with baseline heart rate (P less than 0.05). Compared to standing baseline values, mean plasma norepinephrine and epinephrine levels increased 339% and 301%, respectively, in an integrated 2-min blood sample collected immediately after completion of exercise. Mean adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-EP), beta-lipotropin (beta-LPH), and prolactin levels increased 282%, 720%, 372%, and 211%, respectively, in an integrated 4-min blood sample beginning 2 min after completion of exercise. Cortisol levels increased 183% in the sample collected 17-21 min after exercise. The magnitude of these neuroendocrine responses to exercise was similar among individuals at the same relative intensity of exhaustive exercise, regardless of the duration of exercise. The exercise-induced increases of the pro-opiomelanocortin (POMC)-derived peptides, ACTH, beta-EP, and beta-LPH, were highly correlated with each other (P values less than 0.001), and were correlated with prolactin increases, (P values less than 0.05). During a 20-min recovery period after exercise, changes in heart rate, ACTH, and beta-LPH levels were correlated with duration of exercise, (P less than 0.01, P less than 0.03, and P less than 0.03, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Roles of absolute and relative load in skin vasoconstrictor responses to exercise

Systemic hemodynamic responses to exercise (e.g., heart rate, blood pressure) depend on the relative intensity, the active muscle mass, and the mode of exercise. It is not known whether regional vasomotor responses follow the same pattern. To answer this question, in five men we examined cutaneous vascular responses to dynamic and isometric exercise of two legs, one leg, one arm, and one hand, each at high and low work loads. Skin blood flow was monitored by laser-Doppler flowmetry (LDF) at the forearm. Mean arterial pressure (MAP) was measured each minute. Cutaneous vascular conductance (CVC) was indexed as LDF/MAP. Reductions in CVC during the 1st min of dynamic exercise were statistically significant for two-leg exercise at either level and for one-leg exercise at the higher level. Dynamic exercise of smaller muscle groups at either intensity was not associated with significant changes in CVC. The reduction in CVC correlated with external work load (r = 0.75). Work load relative to the capacity of a given muscle group had no identifiable role in the response of CVC to dynamic exercise but did have a role in the increase in MAP at the beginning of exercise. Isometric exercise did not have a measurable effect on CVC regardless of the muscle group or the intensity of the exercise. We conclude that the level of external work determines the redistribution of blood flow from skin to active muscle. Furthermore, absolute rather than relative work and dynamic rather than isometric modes of exercise are the dominant factors.     

Monocyte and macrophage dysfunction as a cause of HIV-1 induced dysfunction of innate immunity

HIV-1 can establish both long lived and productive infection of macrophages (M?) but circulating monocytes are less permissive to infection. Multiple studies have identified extensive changes to monocyte and M? phenotype, differentiation or function. These include alterations in Toll-like receptor signaling and resultant changes to cytokine responses, specific defects in phagocytosis and microbial killing and modulation of apoptotic responses, all of which may perturb the important role of these cells in innate immunity. Interpretation of contradictory data however, is complicated by the use of different experimental models and many of the reported effects may be an indirect consequence of HIV 1 infection that result from exposure to viral products or from disruption of cellular and cytokine networks in the immune system, rather than the direct consequence of productive HIV 1 infection. Future research should focus on refining experimental models and on elucidating the physiological mechanisms of monocyte/ M? dysfunction during HIV 1 infection.     

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.     

The effects of head cooling on endurance and neuroendocrine responses to exercise in warm conditions

The present study investigated the effects of head cooling during endurance cycling on performance and the serotonergic neuroendocrine response to exercise in the heat. Subjects exercised at 75 % VO(2max) to volitional fatigue on a cycle ergometer at an ambient temperature of 29+/-1.0 degrees C, with a relative humidity of approximately 50 %. Head cooling resulted in a 51 % (p<0.01) improvement in exercise time to fatigue and Borg Scale ratings of perceived exertion were significantly lower throughout the exercise period with cooling (p<0.01). There were no indications of peripheral mechanisms of fatigue either with, or without, head cooling, indicating the importance of central mechanisms. Exercise in the heat caused the release of prolactin in response to the rise in rectal temperature. Head cooling largely abolished the prolactin response while having no effect on rectal temperature. Tympanic temperature and sinus skin temperature were reduced by head cooling and remained low throughout the exercise. It is suggested that there is a co-ordinated response to exercise involving thermoregulation, neuroendocrine secretion and behavioural adaptations that may originate in the hypothalamus or associated areas of the brain. Our results are consistent with the effects of head cooling being mediated by both direct cooling of the brain and modified cerebral artery blood flow, but an action of peripheral thermoreceptors cannot be excluded.     

Blood lactate responses in incremental exercise as predictors of constant load performance

Seven trained male cyclists (VO2max = 4.42 +/- 0.23 l.min-1; weight 71.7 +/- 2.7 kg, mean +/- SE) completed two incremental cycling tests on the cycle ergometer for the estimation of the "individual anaerobic threshold" (IAT). The cyclists completed three more exercises in which the work rate incremented by the same protocol, but upon reaching selected work rates of approximately 40, 60 and 80% VO2max, the subjects cycled for 60 min or until exhaustion. In these constant load studies, blood lactate concentration was determined on arterialized venous ([La-]av) and deep venous blood ([La-]v) of the resting forearm. The av-v lactate gradient across the inactive forearm muscle was -0.08 mmol.l-1 at rest. After 3 min at each of the constant load work rates, the gradients were +0.05, +0.65* and +1.60* mmol.l-1 (*P less than 0.05). The gradients after 10 min at these same work rates were -0.09, +0.24 and +1.03* mmol.l-1. For the two highest work rates taken together, the lactate gradient was less at 10 min than 3 min constant load exercise (P less than 0.05). The [La-]av was consistently higher during prolonged exercise at both 60 and 80% VO2max than that observed at the same work rate during progressive exercise. At the highest work rate (at or above the IAT), time to exhaustion ranged from 3 to 36 min in the different subjects. These data showed that [La-] uptake across resting muscle continued to increase to work rates above the IAT. Further, the greater av-v lactate gradient at 3 min than 10 min constant load exercise supports the concept that inactive muscle might act as a passive sink for lactate in addition to a metabolic site.     

Cardiovascular responses to exercise as functions of absolute and relative work load

The roles of absolute and relative oxygen uptake (VO2 and percent of muscle group specific VO2 max) as determinants of the cardiovascular and ventilatory responses to exercise over a wide range of active muscle mass have not previously been defined. Six healthy men performed four types of dynamic exercise--one-arm curl, one-arm cranking, and one- and two-leg cycling at four different relative work loads--25, 50, 75, and 100% of VO2 max for the corresponding muscle group. VO2 during maximal one-arm curl, one-arm cranking, and one-leg cycling averaged 20, 50, and 75%, respectively, of that for maximal two-leg cycling. Cardiac output was linearly related to VO2 with a similar slope and intercept for each type of exercise. Heart rate at a given %VO2 max was higher with larger active muscle mass. In relation to %VO2 max, systemic resistance was lower and plasma catecholamine levels were higher with larger active muscle mass. The cardiovascular responses to exercise are determined to a large extent by the active muscle mass and the absolute oxygen uptake, with the principal feature appearing to be the tight linkage between systemic oxygen transport and utilization.     

Effect of DENA induced hepatocarcinogenesis on neuroendocrine levels in male rats

Hepatocarcinogenesis was induced in Sprague Dawley rats by injecting diethylnitrosamine (DENA); 150 mg/kg body weight, ip, a well known liver carcinogen and a mutagenic agent. Concurrent with the induction of hepatocarcinoma, psychological stress was also elicited from the changes in brain neurotransmitters. Noradrenaline and dopamine, the neurotransmitters of sympathetic system were estimated from the whole brain and corresponding hormones T3, T4 and prolactin were estimated from the blood of such rats. The neuroendocrine cascade and the marker enzyme gamma glutamyl transferase were estimated at 7, 14, 21 and 30 weeks. A direct relationship between noradrenaline, T3 and T4 and a reciprocal relationship between dopamine and prolactin were observed, which may be correlated to the carcinogenic effect of DENA.     

Autoimmunity and tumor immunity induced by immune responses to mutations in self

Little is known about the consequences of immune recognition of mutated gene products, despite their potential relevance to autoimmunity and tumor immunity. To identify mutations that induce immunity, here we have developed a systematic approach in which combinatorial DNA libraries encoding large numbers of random mutations in two syngeneic tyrosinase-related proteins are used to immunize black mice. We show that the libraries of mutated DNA induce autoimmune hypopigmentation and tumor immunity through cross-recognition of nonmutated gene products. Truncations are present in all immunogenic clones and are sufficient to elicit immunity to self, triggering recognition of normally silent epitopes. Immunity is further enhanced by specific amino acid substitutions that promote T helper cell responses. Thus, presentation of a vast repertoire of antigen variants to the immune system can enhance the generation of adaptive immune responses to self.     

Sympatho-endocrine and metabolic responses to exercise under post-ganglionic blockade in rats

The purpose of this study was to further document the role of locally released norepinephrine (NE) in the control of metabolic and endocrine responses to exercise in rats. Post-ganglionic blockade with bretylium (20 mg.kg-1, i.v.) reduced NE release from sympathetic nerve endings and triggered a compensatory increase in epinephrine (E) release from the adrenal medulla, as reflected by plasma NE and E concentrations at rest and exercise (E/NE ratio = 2.92 +/- 0.53 and 2.48 +/- 0.51 vs 0.62 +/- 0.15 and 1.48 +/- 0.18 in control rats; mean +/- SE). Following bretylium administration a reduction in running time to exhaustion (28 m.min-1, 8% slope: 33 +/- 2 min vs 74 +/- 10 min) was associated with 1) a faster decrease in blood glucose concentration (3.58 +/- 0.80 mM vs 8.09 +/- 0.38 mM in control rats exercised for 33 min); and 2) an increased glycogen store utilization in fast-twitch muscles (superficial vastus lateralis and gastrocnemius lateralis). Glycogen utilization was not modified in soleus muscle and in the liver. Taken together these results suggest that post-ganglionic blockade increased carbohydrate store and peripheral blood glucose utilization. This could reflect an impairment in fat mobilization and utilization which might be secondary to a reduction of NE release in the adipose tissue and/or in the endocrine pancreas.     

Immunomodulations induced in rats by exercise on a treadmill

Various regimens of treadmill exercise (0% slope) were used with rats: 60 min at 15 m/min (T-15), 180 min at 10 m/min (T-10), and 60 min/day at 15 m/min for 6 consecutive days (T-15-6). Exercise resulted in 1) decreases in the absolute number of mononuclear spleen cells in T-10 rats, 2) significant increases in in vitro splenic T-cell blastogenesis in response to phytohemagglutinin in T-10 rats, and 3) significant decreases in T-cell blastogenesis in T-15-6 rats. T-15-6 rats were given aminoglutethimide per os before exercise sessions to study the role of corticosteroids in the alteration of splenic T-cell blastogenesis. Aminoglutethimide significantly increased the T-cell blastogenesis in these T-15-6 rats compared with those not given aminoglutethimide, whereas it had no effect on immune parameters of sedentary rats. These results show that immunomodulations in the rat depend on the treadmill exercise regimen employed. If the mechanisms of the immunomodulation induced by isolated exercise of long duration are not elucidated, these data suggest that corticosteroids are involved in the alteration in T-cell blastogenesis induced by chronic muscular exercise.