Biomedical subjects
M J Fregly
Publications and source records attributed to M J Fregly.
Metabolic responsiveness of spontaneously hypertensive rat to isoproterenol.
The metabolic responsiveness of spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) normotensive rats to administration of the beta-adrenergic agonist, isoproterenol, was assessed by changes in tail-skin temperature, heart rate, and plasma glucose concentration after administration of graded doses of isoproterenol. The increases in mean tail-skin temperature accompanying administration of isoproterenol at doses of 5, 10, and 40 micrograms/kg sc were significantly (P less than 0.05) greater for SH than for WKY rats. Resting colonic temperatures of the SH rats were also significantly (P less than 0.01) higher than those of the WKY normotensive rats. Mean maximal heart rates of unanesthetized SH rats after administration of isoproterenol at doses of 5, 10, and 20 micrograms/kg sc increased to levels significantly (P less than 0.05-0.01) higher than those of WKY normotensive rats. Resting heart rates were similar in both groups. Increases in plasma glucose concentration after administration of isoproterenol at doses of 5, 10, and 20 micrograms/kg sc were significantly (P less than 0.05) greater in the SH rats compared with the WKY rats. These results suggest that the SH rat has a significantly greater metabolic responsiveness to beta-adrenergic stimulation, as assessed by three separate tests of beta-adrenergic function, than does the WKY rat.
Proposed mechanism for increased thyroxine deiodination in cold-acclimated rats.
Groups of male rats were administered isoproterenol (ISO), thyroxine (T4), or both (ISO + T4) daily for 20 days in an attempt to mimic the effect of cold acclimation on the rate of outer-ring deiodination of T4 to triiodothyronine (T3) by 2,000-g supernatants of homogenates of liver and kidney. The rates of hepatic and renal deiodination of T4 to T3 in an additional group of rats exposed to 4 +/- 1 degree C for 20 days were 53 and 71% higher, respectively, than control. Administration of ISO (100 micrograms . kg-1 . day-1) did not affect the rate of deiodination of T4 to T3 by either hepatic or renal tissue. Administration of T4 (50 micrograms . kg-1 . day-1) resulted in rates of hepatic and renal deiodination of T4 that were 297 and 222% higher, respectively, than control. Administration of ISO + T4 resulted in a rate of conversion of T4 to T3 not significantly different from that observed when T4 was administered alone. Serum concentration of T4 was elevated after administration of both T4 and ISO + T4, whereas serum concentration of T3 was elevated significantly above that of control only in the cold-acclimated group. These results suggest that the increased rate of 5'-monodeiodination of T4 by hepatic and renal homogenates from cold-acclimated rats is not a result of increased beta-adrenergic activity but can be accounted for by the increase in thyroid activity observed in these animals.
Use of lactoperoxidase-catalyzed iodination of L-tyrosine to assess antithyroid activity of a factor present in certain tissues of mammals.
A factor, present in the kidneys of rats, has been shown to inhibit thyroid activity both in vivo (rat) and in vitro (porcine and bovine thyroid slices). The aim of the present study was to quantitate the inhibitory activity of this factor in renal and other tissues from rats by means of the lactoperoxidase-catalyzed iodination of L-tyrosine. Supernatants of renal homogenates (10,000, 27,000 and 35,000 g) obtained from rats inhibited this in vitro iodination system as well as the lactoperoxidase-catalyzed oxidation of guaiacol. The 35,000-g supernatant from both renal and hepatic tissues contained the greatest inhibitory activity per milligram of protein. Supernatants of homogenates (35,000-g fraction) from testes contained one eighth to one third the activities of liver and kidney, respectively. Kidneys of other species including fetal goat, mature goat, fetal lamb, mature monkey and mature dog, were also shown to contain the thyroid-depressing factor. These studies suggest that the thyroid-depressing factor is found mainly in liver and kidneys of the rat and that it is not unique to the rat but is present in the kidneys of other species as well.
Effect of the angiotensin-converting enzyme inhibitor, captopril, on development of renal hypertension in rats.
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Effect of captopril on the blood pressure response to angiotensin I in turkeys.
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Catecholamine-mediated diuresis in turkeys.
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Attenuation of isoproterenol-stimulated plasma renin activity by chronic estrogen treatment.
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Dipsogenesis in cold-acclimated rats.
Water intakes of control rats kept at 25 degrees C and cold-acclimated rats kept at 6 degrees C for at least 4 weeks were compared when both groups were at 25 degrees C. Cold-acclimated rats exhibited an increase in water intake (thermogenic drink) during the first but not the second hour after removal from the cold. Cold-acclimated rats, administered the dipsogenic agents angiotensin I, angiotensin II, isoproterenol or serotonin, had water intakes not significantly different from control rats. Administration (1% of body weight) of several different doses of hypertonic NaCl (0.25 to 1.00M) intraperitoneally increased water intake to the same level in both control and cold-acclimated rats. Water deprivation for 24 h, initiated either 2 or 24 h after removal of cold-acclimated rats from the cold, resulted in water intakes not significantly different between cold-acclimated and control rats. In spite of an initial thermogenic drink on removal of cold-acclimated rats from cold, cold-acclimation does not appear to alter the dipsogenic responsiveness of rats to either extracellular or intracellular dipsogenic stimuli, or to a dipsogenic stimulus (dehydration) involving both.
Effect of chronic treatment with estrogen on the dipsogenic response of rats to angiotensin.
Female rats treated with estradiol benzoate for 23 weeks at doses of 25 and 44 microgram/kg/day had an attenuated drinking response to peripheral administration of graded doses of angiotensin I and angiotensin II. No significant difference between the responses of the two estrogen-treated groups was observed, suggesting that maximal attenuation had been attained with the lower dose. Angiotensin II (50, 100 and 200 microgram/kg, IP) increased urine output and urinary sodium excretion rate in a graded fashion with increasing doses in both control and estrogen-treated rats. However, the latter had a somewhat greater response. Administration of angiotensin I (50, 100 and 200 microgram/kg, SC) had a similar, but less consistent, effect on urine output and urinary sodium excretion rate in both control and estrogen-treated groups. The attenuated drinking response of estrogen-treated rats to angiotensin I and angiotensin II suggests either that administered angiotensin failed to gain access to the brain or that central receptors mediating thirst are less sensitive in estrogen-treated rats. The present studies fail to distinguish between these possibilities.
beta-adrenergic responsiveness of rats treated chronically with isoproterenol.
The effect of chronic administration of isoproterenol on isoproterenol-induced thirst and isoproterenol-induced changes in heart rate and selected organ weights of male rats was studied. Administration of 25 micrograms isoproterenol/kg, s.c., in saline daily for 10 days was accompanied by a significant attenuation of the characteristic increase in water intake following a challenging dose of isoproterenol (25 micrograms/kg, s.c.) on the 11th day. Administration of 25 micrograms isoproterenol/kg, s.c., every 2nd, 3rd or 4th day for 10 days was without significant effect on water intake following isoproterenol (25 micrograms/kg, s.c.) on the 11th day. Administration of 25 micrograms isoproterenol/kg, s.c., every day for 10 days led to a slight increase in cardiac responsiveness to a challenging dose of isoproterenol (25 micrograms/kg) on the 11th day. Chronic treatment with this low dose of isoproterenol for 10 days was also accompanied by a significant increase in the ratio of heart weight to body weight but no significant changes in the ratio of kidney, adrenal, thyroid, spleen, or interscapular brown fat to body weight. Thus, daily administration of the beta-adrenergic agonist isoproterenol for 10 days can alter beta-adrenergic responsiveness in the rat with beta 1 (heart rate) and beta 2 (thirst) mediated responses showing opposite effects. In addition, the results suggest that tests of beta-adrenergic responsiveness must be assessed in terms of the frequency of administration of the agonist.
In vitro hepatic deiodination of L-thyroxine to 3,5,3'-triiodothyronine in cold-acclimated rats.
An in vitro model has been employed to evaluate the effect of cold acclimation on peripheral outer ring deiodination of thyroxine (T4) to triiodothyronine (T3) by 9,000 g supernatants of fresh liver homogenates. Hepatic T3 generation from T4 in male rats exposed to 4 +/- 1 degree C for 12 wk was 41 and 24% higher than control after 30- and 60-min incubation periods, respectively. This was associated with a 49% increase in serum T3 concentration in the cold-acclimated rats, whereas serum T4 concentration did not differ from the control. Thus, hepatic deiodination of T4 appears to serve as an important source for production of T3 during cold acclimation. It is suggested that the increased beta-adrenergic activity observed previously in cold-acclimated rats stimulates this change.
Changes in beta-adrenergic responsiveness of rats during chronic cold exposure.
Administration of isoproterenol (50 micrograms/kg sc) to rats that had been exposed to cold (6 degrees C) for 10, 15, and 25 days was accompanied by a greater increase in tail skin and colonic temperatures than in controls kept at 25 degrees C. Administration of isoproterenol (8 micrograms/kg sc) to cold-treated rats (1, 3, 5, 7, 14, and 28 days) increased heart rates above that of controls. However, resting unstimulated heart rates of cold-treated rats were also increased above that of controls after 1, 3, 5, and 7 days of cold exposure but were not different from controls after 14 and 28 days. Cold exposure also led to time-dependent increases in the weights of heart, adrenals, and interscapular brown fat. Thus, chronic exposure of rats to cold is accompanied by an increase in responsiveness of both heart rate and tail skin and colonic temperatures to beta-adrenergic stimulation. The results also suggest that increases in responsiveness to a beta-adrenergic agonist may not occur at the same time for the different beta-adrenergic-mediated metabolic and cardiovascular responses in cold-treated rats.
Effect of isomers of octopamine on in vitro reactivity of vascular smooth muscle of rats.
The vascular reactivity to DL-ortho-, meta-, and para-octopamine was tested in vitro in aortic smooth muscle of the rat. When reactivities were compared on a molar basis with L-phenylephrine, an alpha-adrenergic agonist, the potencies of the three isomers were: 0.7500, 0.0075 and 0.0038 times that of phenylephrine for the m-, p- and o-isomer, respectively, Thus, of the three isomers, DL-m-octopamine had the greatest alpha-adrenergic activity in vitro as it did in vivo in earlier studies. Additional studies showed L-phenylephrine to induce about one-third the vascular response induced by L-norepinephrine.
Attenuation of pilocarpine-induced drinking by chronic treatment with estrogens.
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The effect of acute administration of an angiotensin converting enzyme inhibitor, captopril (SQ 14,225), on experimentally induced thirsts in rats.
In order to assess the role of angiotensin in the genesis of certain types of thirst, rats were administered the angiotensin converting enzyme inhibitor, captopril, in an attempt to block the increased water intake induced either by water deprivation or by i.p. administration of hypertonic saline. Water deprivation for 24 hr resulted in an increased water intake. Acute administration of 50 mg of captopril per kg i.p. at 45 or 60, but not at 15 or 30, min before return of water to the dehydrated rats significantly attenuated the drinking response. Rats administered 1% b.wt. i.p. of 0.25, 0.50, 0.75 or 1.00 M NaCl solution increased proportionately their water intake. Acute administration of 35 mg of captopril per kg b. wt. i.p. 15 min before loading with NaCl solution at any of the above concentrations had no effect on the increased thirst induced. These findings suggest that hypertonic saline-induced thirst is not mediated by angiotensin II receptors while water deprivation-induced thirst may involve both osmoreceptors and angiotensin II receptors.
Effect of the angiotensin converting enzyme inhibitor, captopril, on NaCl appetite of rats.
Dietary administration of the angiotensin converting enzyme inhibitor, captopril (0.70 g/kg of food), to female rats for 1 week was accompanied by a spontaneous appetite for 0.25, 0.30 or 0.35 M NaCl solution when choice was offered between any one of them and distilled water to drink. An additional experiment was performed to determine the NaCl preference threshold concentration for each group. Control and treated rats were offered choice between two drinking bottles containing distilled water and a NaCl solution, respectively. The concentration of the latter varied from 0.0006 to 0.350 M/l. Control rats could detect the difference between water and NaCl solution at a concentration of 0.030 M/l, whereas captopril-treated rats detected the difference at the lowest concentration offered, i.e., 0.0006 M/l. Captopril-treated rats also preferred 5% glucose solution to distilled water, as did untreated controls. Similar results were observed for 0.25% saccharin. No difference between groups was observed when choice was offered between distilled water and dilute solutions of HCl. Thus, a NaCl appetite developed within 1 week of treatment with captopril. The appetite was accompanied by an ability to detect NaCl at a 50-fold lower concentration than that of the control group. Administration of captopril was also accompanied by an appetite for glucose and saccharin but not for HCl.
Influence of thyroactive iodinated casein on B-aminopropionitrile-induced aortic ruptures of turkeys.
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