Search PubMed⌕ Search

Biomedical subjects

M J Fregly

Publications and source records attributed to M J Fregly.

At least 199 records · Page 11Linked to original sources

Inhibition of thermogenic drinking by beta-adrenergic antagonists.

The thirst induced by transfer of rats from air at 5 degrees C to air at 25 degrees C (thermogenic drink) was inhibited by d,1-, but not d-propranolol (6 mg/kg body weight) administered 0.5 h prior to removal from cold. The thermogenic drink was not inhibited by a similar administration of the beta1-adrenergic antagonist, practolol (50 and 150 mg/kg body weight), but was inhibited by the beta2-adrenergic antagonist, butoxamine (35 mg/kg body weight). The results are consistent with the suggestion that beta2-adrenergic receptors play a role in mediation of the thermogenic drink in rats.

Adrenergic beta-Antagonists↗

Effect of chronic exposure to cold on some responses to catecholamines.

An objective of these studies was to test the responsiveness of cold-adapted (8 wk, 5 degrees C) rats to a specific beta-adrenergic agonist. Twenty-four hours after removal from cold, increases in tail skin temperature (Tsk) and colonic temperature (Tco) were measured for 2 h in air at 25 degrees C following subcutaneous (sc) administration of 28, 70 or 136 mug d,l-isoproterenol sulfate dihydrate/kg body wt to restrained male rats. Cold-adapted rats responded to each dose of isoproterenol with greater increases in Tsk than controls. Tco of both groups increased at the two highest doses, but cold-adapted rats showed a greater rise. Thus, cold-adapted rats showed greater metabolic (Tco) and vascular (Tsk) responsiveness to the beta-adrenergic agonist, isoproterenol, than nonadapted controls. No effect of the alpha-adrenergic agonist, phenylephrine (50 or 100 mug/kg body weight, sc), was observed on Tco or Tsk. A second objective was to study the tension developed by aortic smooth muscle rings of cold-adapted and control rats both during stimulation of alpha-adrenergic receptors by norepinephrine and membrane depolarization by KCl. Adaptation to cold air appeared to suppress alpha-adrenergic responsiveness in aortic segments but did not alter responsiveness to KCl. This suggests an unchanged contractile mechanism in aortic rings of cold-adapted rats and a reduced responsiveness either at the level of the alpha-receptor or at a site immediately beyond.

Adaptation, Physiological↗

Effect of some substituted pyrimidines on development of desoxycorticosterone-induced hypertension in rats.

Chronic (15-week) dietary administration of 2-thio-6-aminouracil (TAU, 1.0 and 2.0 g/kg food) provided significant protection against elevation of blood pressure and cardiac hypertrophy in male rats treated with desoxycorticosterone trimethylacetate (DTMA) (5.0 mg twice weekly for 10 weeks). Assessment of thyroid activity was made by measurement of 24 h 131I uptake by the thyroid gland, PBI concentration of serum, rate of oxygen consumption, hematocrit ratio, hemoglobin concentration, and thyroid weight. By all these criteria, the rats given either dose of TAU were hypothyroid. In contrast chronic (17-week) dietary administration of 5-carboxy-2-thiouracil (0.50 and 1.00 g/kg food) and 5-carboxy-4-hydroxy-2-thiouracil (2.00 g/kg food) provided minimal protection against elevation of blood pressure and cardiac hypertrophy in male DTMA-treated rats. These compounds appeared to possess little or no antithyroid activity at the doses used. The results suggest a rough correlation between the degree of hypothyroidism produced by the compounds and their effectiveness in preventing rise of blood pressure in DTMA-treated rats.

Animals↗

Response of heart rate to acute administration of isoproterenol in rats treated chronically with norethynodrel, ethinyl estradiol, and both combined.

Chronic (17 to 20 weeks) administration of ethinyl estradiol alone (36 mug/kg/day), and in combination (27 or 50 mug/kg/day) with several doses of norethynodrel (135, 165 or 233 mug/kg/day), attenuated the increase in heart rate accompanying acute SC administration of the beta-adrenergic agonist, l-isoproterenol (50 or 100 mug/kg), to female rats. Dietary administration of an oral contraceptive containing mestranol and norethynodrel (7.5 mg/kg/food) was also accompanied by an attenuated response to isoproterenol. A significant inverse linear relationship was observed between the logarithm of the dose of estrogen received by each group and either heart rate or change in heart rate measured at 10, 20 and 30 min after administration of isoproterenol. Thus, the antagonistic relationship between the dose of estrogen administered chronically and responsiveness of heart rate to a test dose of isoproterenol suggests a reduced beta-adrenergic responsiveness in estrogen-treated rats.

Animals↗

Increased responsiveness of heart rate to beta-adrenergic stimulation in cold-adapted rats.

The responsiveness of heart rate of cold-adapted rats (10-12 weeks, 5degrees C.) to a specific beta-adrenergic agonist was studied. Two hours after removal from cold, s.c. administration of l-isoproterenol (4, 8, or 16 microng/kg body weight) to female rats was accompanied by a greater responsiveness in cold-treated animals. The increase in heart rate of cold-treated rats above that of warm-adapted controls was related linearly to the dose of isoproterenol administered. An increased sensitivity of heart rate to isoproterenol (8 microng/kg body weight, s.c.) was also observed in male, cold-treated rats. The results suggest that adaptation to cold air is accompanied by increased beta-adrenergic responsiveness in rats.

Adaptation, Physiological↗

Responsiveness to various dipsogenic stimuli in rats treated chronically with norethynodrel, ethinyl estradiol and both combined.

Administration of the estrogen, ethinyl estradiol (36 microng/kg/day), alone, and in combination with the progestogen, norethynodrel (165 microng/kg/day), significantly attenuated the dipsogenic response characteristically induced by acute s.c. administration of the beta adrenergic agonist, dl-iosproterenol (50 microng/kg). Attenuation was apparent within 1 week of steroid treatment, and remained during the 4 weeks of testing. After 16 weeks of steroid treatment, the drinking response to acute i.p. administration of renin (2 and 4 Goldblatt units/rat) was tested. The groups receiving ethinyl estradiol alone, and in combination with norethynodrel, but not norethynodrel alone, showed a reduced water intake compared with untreated controls. Drinking induced by administration of hypertonic saline (1% of body weight of 1 M NaCl solution, i.p.) was also reduced in rats treated with the estrogenic, but not the progestational, agent. However, estrogen treatment did not affect drinking after a 24-hour period of dehydration. Although the reduced dipsogenic response to isoproterenol observed in estrogen-treated rats may reflect a reduced renin secretion, drinking could not be induced in these animals by administration of renin. In addition, the reduced dipsogenic response to hypertonic NaCl loading suggests that estrogens may inhibit thirst mechanisms centrally. Dehydration, which combines hypovolemic and osmotic thirst situmul was, however, sufficient to overcome the reduced dipsogenic responsiveness of estrogen-treated rats.

Animals↗

Effect of hypothyroidism on responsiveness to beta-adrenergic stimulation.

Chronic administration of aminotriazole (0.5 g/kg food) to rats was accompanied by a reduced responsiveness to acute administration of the beta-adrenergic agonist, l-isoproterenol (50-100 mug/kg, sc). The responses tested included water intake, change in heart rate in the anesthetized and unanesthetized rat, change in mean blood pressure, and change in blood glucose concentration. In addition, the increase in tail skin temperature accompanying administration of epinephrine (1 mg/kg, sc) was significantly reduced in the hypothyroid group. Administration of l-thyroxine (25 mug/kg per day, ip) to aminotriazole-treated rats prevented the reduction in responsiveness to beta-adrenergic stimulation. Thus, an interaction appears to exist between the level of thyroid activity and responsiveness to beta-adrenergic agonists in rats.

Adrenergic beta-Agonists↗

Effect of water temperature during cold exposure on thermogenic drinking in rats.

Availability of water at temperatures higher than ambient (15, 25, 35 degrees C) failed both to affect the ratio of water to food intake during exposure to cold air (5 degrees C) and to influence the thermogenic (postcold exposure) drinking response of rats which characteristically occurs immediately after removal from cold air. Thus, availability of warm water during exposure to cold appeared to have no influence on cold-induced dehydration in rats. A specially constructed drinking apparatus was used in this study. It was designed to maintain water at temperatures greater than ambient during exposure to cold. Details for construction of the apparatus are provided.

Animals↗

Reduced beta adrenergic responsiveness in rats treated with estrogenic agents.

Chronic treatment with ethynyl estradiol alone (48-50 mug/kg/day) and in combination with several doses of norethynodrel either attenuated or prevented the increase in tail skin temperature accompanying sC. administration of isoproterenol (200 mug/kg b.wt.) to male and female rats. Dietary administration of an oral contraceptive containing norethynodrel and mestranol (7.5 mg/kg of food) was also accompanied by an attenuated response to isoproterenol. Attenuation of the tail skin temperature response was present in all groups after 3 to 5 weeks of treatment but was detectable in the oral contraceptive-treated group after 1 week of treatment. All steroids and combinations, except norethynodrel administered alone (154 mug/kg/day), reduced body weight gain.

Animals↗

Water exchange in rats exposed to cold, hypoxia, and both combined.

Male rats were exposed chronically to cold (5 degrees C air), hypoxia (12% oxygen in nitrogen), and both combined. Intake of water and food, as well as urinary excretion, were measured during both a 5-d pretreatment control period and throughout the first 3 weeks of the treatment period. Regression analysis of water intake on urine output revealed that, at a given water intake, all three treated groups excreted significantly more urine than controls. No significant differences occurred among treated groups. Serum osmolalities of all three treated groups, measured at the end of the 48-d treatment period, were elevated significantly above the level of the control group. All treated groups also manifested a thirst immediately following return to control environment (26 degrees C, 20.9% oxygen). Water intakes of all three treated groups were significantly greater than that of the control group during the first 2 h after return to control environment. Thus, the three treated groups appeared to be dehydrated relative to the control group. The results further suggest that the effect of combined cold (5 degrees C) and hypoxia (12% oxygen) on water exchange is not a summation of that occurring separately during cold and hypoxia. The factors inducing dehydration in cold and hypoxia are apparently related to increased evaporative water loss and to alterations in thirst and renal mechanisms.

Animals↗

Factors affecting thermogenic drinking in rats.

After as little as 6 h of exposure to cold air, drinking was induced in rats following transfer from air at 5 degreesC to air at 26 degreesC. Drinking began within 15 min after transfer from the cold enviroment and lasted approximately 1 h. The stimulus for initiation of drinking was most likely the temperature change resulting from the transfer, since an ambient temperature difference of 10 centigrade degrees or more was required to initiate a drinking response after transfer from air at 5 degreesC. Thermogenic drinking was not thwarted by preventing access to water for either 1 or 2h following transfer to warm air, but either intragastric or intraperitoneal administration of a water load equal to 3% of body weight inhibited water intake following transfer.The characteristics of the drinking response following transfer than 5 to 26 degrees C were similiar to those observed following 24 h of dehydration at 26 degrees C. Thus, the cold-exposed rat is relatively dehydrated compared with controls.

Animals↗

Reduced beta-adrenergic responsiveness in hypothyroid rats.

The beta-adrenergic agonist isoproterenol (100-200 mug/kg body wt sc) induces vasodilation and an increase in skin temperature of the tail of the euthyroid but not the hypothyroid rat. Administration of thyroxine (25 mug/kg body wt per day) to rats made hypothyroid by means of the antithyroid drug aminotriazole (0.5 g/kg of foof) returned responsiveness to control level. Reduced responsiveness to isoproterenol occurred between 1 and 5 wk of treatment with aminotriazole. Increase in tail skin temperature induced in euthyroid rats by isoproterenol was blocked by administration of propranolol (7.5 mg/kg ip). Other beta-adrenergic-induced responses, including increased water intake and increased plasma glucose concentration, also were reduced in hypothyroid rats and returned to control level by administration of thyroxine. Thus, hypothyroidism appears to be accompanied by a reduced beta-adrenergic responsiveness as assessed by changes in tail skin temperature, water intake, and plasma glucose concentration after injection of isoproterenol. Since administration of thyroxine returned the responses of hypothyroid rats to control levels, it appears that thyroxine is important in maintaining beta-adrenergic responsiveness under these conditions.

Animals↗

Peripheral body temperature and thermogenic drinking in cold-treated rats.

Transfer of rats abruptly from air at 5 degrees C to air at 26 degrees C was accompanied by a significant increase in water intake (thermogenic drinking) during the first hour after transfer. A possibility existed that the increased water intake observed under these conditions was attributable to the rapid change in skin temperature. Thus, the objective of this study was to determine the effect on thermogenic drinking of a slow, as opposed to an abrupt, change in ambient temperature. The results indicated that warming room air rates of either 0.5 or 1.0 centigrade deg/min had no effect on thermogenic drinking when compared with the water intake of rats removed abruptly from cold. Thermogenic drinking does not appear to be initiated by a specific pattern of changes in peripheral temperature relative to colonic temperature.

Acclimatization↗