Centrally administered PD 140.548 N-methyl-D-glucamine prevents the autonomic responses to duodenal pain in sheep.

Cholecystokinin (CCK) released in the CNS inhibits the analgesic action of exogenous opioids and may antagonize analgesia resulting from the activation of an endogenous pain inhibitory system. The aim of this study was to analyse the central action of PD 140.548 N-methyl-D-glucamine--a peptide antagonist of a specific peripheral type CCK receptor--on animal behaviour, catecholamines (CA) and cortisol concentration, as well as clinical symptoms of visceral pain induced by duodenal distension (DD). A 5 min distension of the duodenum wall, using a 10 cm long balloon filled with 40 and/or 80 ml of water (DD 40 and/or DD 80) at animal body temperature, produced a significant increase in plasma CA and cortisol levels, an increase in the heart rate, hyperventilation and other clinical symptoms (inhibition of rumen motility, bleating, teeth grinding, prostration, urination, defecation) that may be related to pain, proportionally to the degree of intestinal distension. Intracerebroventricular administration of PD 140.548 at the dose of 1 or/and 2 mg in toto 10 min before applying DD 40 completely blocked the increase in blood plasma cortisol, epinephrine (E), norepinephrine (NE) and dopamine (DA) concentration. It is suggested that the central inhibitory action of CCK antagonist on the cortisol and catecholamine release produced by visceral pain is due to the inhibition of peripheral CCK1 type receptors in the central centrifugal descending pain facilitatory system in sheep perhaps via the hypothalamic-pituitary-adrenal axis.

Enhanced non-esterified fatty acids and corticosterone in blood plasma of chickens treated with insulin are significantly depleted by reverse T: minor changes in hypoglycaemia.

Previously, it has been observed that dexamethasone or adrenaline-induced hyperlipaemia in blood of chicken was significantly reduced after administration of reverse triiodothyronine (rT3). The present experiment was performed on chicken to determine the altered circulating non-esterified fatty acids (NEFA) induced by physiologically enhanced endogenous corticosterone and catecholamines may also be influenced by rT3. Rise of both hormones were induced by insulin administration. Changes in circulating glucose, corticosterone and catecholamines were additionally measured. Following insulin injection blood glucose fell on the average by 32.7% below control at 2 h of the experiment. Additional treatment with rT3 (rT3 + insulin group) gradually attenuated this decrease and at 4 and 6 h of the experiment it was 17.1% and 12.9% below control, respectively, suggesting on slight inhibition by rT3 of insulin-stimulated glucose utilization. Exposure to insulin significantly increased NEFA levels to about 670% above control group. Additional treatment with rT3 reduced this increase to 309% of control, suggesting inhibition of lipolysis by rT3. Similar alterations were observed in plasma corticosterone levels. Insulin treatment peaked the corticosterone levels maximally by 507.6% above control. Additional treatment with rT3 abolished this rise in the averages to 194.2% above control, possibly by interaction of rT3 with hypothalamo-adrenal axis. Insulin injection increased plasma catecholamines on the average by 21.5% and 53.4% for adrenaline and noradrenaline respectively. Supplementary treatment with rT3 intensified this rise by 55.6% and 71.6% respectively. The obtained results suggest on inhibitory effect of rT3 on hypoglycaemia, hyperlipaemia and plasma corticosterone concentrations in chickens treated with insulin. Contrary to this, rT3 enhanced the rise of plasma catecholamines due to insulin treatment. The obtained data favour the assumption that hypometabolic properties of rT3 depends mainly upon reduced supply of NEFA as a result of restricted lipolysis and to a lesser extent upon the supply of glucose.

Acute reserpine treatment alters the catecholamine, glucocorticoid and opioid response to walking exercise in sheep.

The aim of the study was to examine the effects of reserpine on the plasma levels of adrenaline, noradrenaline, cortisol and alpha-neoendorphin in sheep under control conditions and during walking exercise. One hour of walking (5 km/h) caused a significant increase in both catecholamines and cortisol between 10 and 30 min of stress, and transiently decreased the level of alpha-neoendorphin at the same time. Reserpine at the dose of 0.3 mg/kg i.v. given before stress significantly lowered the basal levels of all tested parameters. A combination of the reserpine and walking exercise significantly attenuated the stress-induced changes in the plasma level of measured hormones.

Responses of heat stressed chickens to exogenous reverse triiodothyronine (rT3).

Heat stress is accompanied by a decrease in basal metabolic rate and plasma thyroid hormones. Unlike 3,5,3'-triiodothyronine (T3) and thyroxine (T4), 3,3',5'-triiodothyronine (rT3) displays hypometabolic properties and antagonizes the hypermetabolic effect of T3. This study analyses the role of rT3 in heat (38-39 degrees C) stressed immature chickens. Two experiments which differed in frequency of rT3 injections (one or two times a day), duration of heat stress (72 or 48 h) and blood sampling were performed. The dose was 14 micrograms rT3/100 gb.wt./injection (s.c.). It has been shown that rT3 treatment aggravates heat stress symptoms (enhances circulating corticosterone, catecholamines and free fatty acids) and increases mortality. The critical survival time of the rT3 treated and heated birds was at first 24 h of stress. No more chickens died during the next days of the experiment despite the continuation of rT3 injection, suggesting that rT3 might disturb the adaptation to heat. Reverse T3 in heat stressed chickens led to the highest reduction in food consumption (69.9%) and body weight gain (14.0% compared to initial weight). The opposite effect in water consumption (216.9%) was observed. In a neutral environment, rT3 significantly suppressed body temperature 6 h after injection (40.4; control; 41.1 degrees C), confirming its hypometabolic properties. However, at the same time rT3 significantly enhanced body temperature in heat stress (43.03 versus heated control 42.56 degrees C). In addition, in rT3 treated birds decreased plasma triglycerides (TG; 24.3%) and increased plasma free fatty acids (FFA; neutral temperature; 26.4% heat stress: 57%) were demonstrated. A correlation between corticosterone and FFA (r = 0.52) shows that some of the FFA may originate from lipolysis since hormones of the pituitary-adrenocortical axis accelerate lipolysis. The remaining part of the increased FFA appears to be due to suppressed utilization of FFA as a consequence of hypometabolic properties of rT3. Low and negative relation between TG and FFA (r = -0.26; P < 0.05) may support such an assumption. The two times higher peak of corticosterone in the rT3 and the overheated group, as compared to the heated control, occurred at 6 h of heat stress and indicates that rT3 increases the unfavourable effect of high temperature. This was also confirmed by elevated plasma adrenaline and noradrenaline in rT3-injected and heated chickens (55.5 and 120%, respectively). However, a single and two times higher peak of adrenaline at 24 h of heat stress was observed in saline treated birds, but not in rT3 supplemented animals, suggesting that this difference might explain one of the factors responsible for high mortality. In conclusion, the results obtained demonstrate that physiological doses of rT3, a hypometabolic hormone, enhance the unfavourable effect of heat stress in chickens.

Response of sympatho-adrenal axis and adrenal cortex to short-term restraint stress in sheep.

The sympatho-adrenal and pituitary-adrenal cortex axes are the most sensitive, and specific indicators of stress in animals. Increased plasma levels of catecholamines and glucocorticoids are generally considered as the classical response to stress. Most experiments on immobilization have been performed on rats and only a few of them concerned domestic animals. In this experiment we want to learn whether short-term restraint-a stressor most commonly used in animal husbandry-is a stressor for sheep (ewes) like in rats. For this reason we measured adrenaline (A), noradrenaline (NA) (radioenzymatic method), cortisol (RIA method), glucose and free fatty acids (FFA). Unlike in rats, in stressed sheep the peak of A appeared earlier than the NA peak, i.e. at 2 and 5 min. of stress, respectively. In contrast to rats, the basal and stress levels of NA exceeded the corresponding level of A. Cortisol concentration rose 7 fold above baseline and maximal concentration appeared at a time (15-30 min.) observed in other animal species. A similar time-related increase was observed in the plasma FFA concentration. It increased maximally 3.2 fold at 15 min. of stress. A significant correlation coefficient was found between plasma cortisol and FFA (r = 0.91) what may suggest the lipolytic effect of ACTH and/or a positive feedback of FFA on the hypophysis-adrenal axis. The plasma glucose of stressed animals rose only 1.47 fold above the basal level. A significant correlation was found between cortisol and glucose (r = 0.53) whereas no correlations have been obtained between A, NA and glucose or FFA.(ABSTRACT TRUNCATED AT 250 WORDS)

Modified responses of circulating cortisol, thyroid hormones, and glucose to exogenous corticotropin and thyrotropin-releasing hormone in food-deprived sheep.

In a previous experiment, food deprivation was found to suppress the increase of plasma cortisol and thyroid hormones in stressed animals. Because both the hypothalamo-adrenocortical and the thyroid axes are stimulated during stress, we investigated in this study whether a similar pattern of changes occurs in food-deprived sheep following corticotropin (ACTH) or thyrotropin-releasing hormone (TRH) administration. Each hormone was given as a bolus injection on the fifth day of food deprivation. Blood was sampled by venipuncture five times: 0.5 h before and 1, 3, 5, and 9 h after injection of the hormone. The peak of plasma cortisol in food-deprived sheep following ACTH administration exceeded fourfold the corresponding peak in fed animals. This suggests that food deprivation may enhance the sensitivity of the adrenocortical gland to ACTH and/or reduce binding sites for cortisol in target tissues. In fed animals, TRH was without effect on plasma cortisol level, whereas in food-deprived sheep cortisol transiently increased 2.5-fold, suggesting greater permeability of the blood-brain barrier for TRH. In food-deprived animals, plasma T3 was decreased to 22.6% of basal level, and elevated plasma cortisol after ACTH injection was not able to decrease it further. On the other hand, in fed sheep increased plasma cortisol did decrease plasma T3 as much as 4.2-fold. Circulating T4 was not affected by ACTH treatment. The delta increase of plasma T3 and T4 following TRH administration was comparable in fed and fasted animals.(ABSTRACT TRUNCATED AT 250 WORDS)