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M J Fregly

Publications and source records attributed to M J Fregly.

At least 145 records · Page 8Linked to original sources
PubMed1983

Kidney structure in hypothyroidism.

Hypothyroidism is associated with changes in renal function and a decrease in kidney weight. The present study was carried out for examination of the effect of the antithyroid drug aminotriazole (ATZ) on kidney structure and especially for determination of whether hypothyroidism affects the whole nephron or only a specific segment of it. Female Sprague-Dawley rats received ATZ in their diet, 0.5 g/kg food for 4 weeks. Control rats received a normal diet. Additional groups of animals receiving ATZ in the diet were given daily injections of L-thyroxine (T4) for determination of whether ATZ-induced changes could be prevented by thyroid hormone. After collection of physiologic data the kidneys were fixed by in vivo perfusion with 3% glutaraldehyde in preparation for light-microscopic morphometry. Following ATZ treatment there was a significant decrease in serum triiodothyronine (T3) and in GFR. Kidney weights were decreased, mainly because of a reduction of cortical tissue. Morphometry showed no changes in the relative volumes of the various compartments of the kidney, indicating that the decrease in weight involved all segments of the nephron. Direct measurements of tubular diameters revealed a decrease in the peritubular diameters in both proximal tubules and the thick ascending limb and a decreased cell height in the thick ascending limb. All the ATZ-induced changes could be prevented by simultaneous treatment with T4, suggesting that the changes were caused by the antithyroid effect of ATZ and were not a nonspecific toxic effect.

Amitrole↗
PubMed1982

Bethanechol-induced water intake in rats: possible mechanisms of induction.

Acute administration of the parasympathomimetic agent, bethanechol, at 2, 4, 8 and 12 mg/kg body wt, IP, induced drinking and increased urine output of rats in a dose-dependent fashion. The first significant increases in both water intake and urine output above that of controls occurred when 4 mg/kg was administered. The drinking and increased urine output in response to administration of 8 mg bethanechol/kg was inhibited by atropine sulfate (3 and 6 mg/kg, IP). In addition, the beta-adrenergic antagonist, propranolol (6 mg/kg, IP, administered 30 min prior to treatment with bethanechol), inhibited bethanechol (8 mg/kg, IP)-induced drinking. Urine output, however, was unaffected by propranolol. Further, the angiotensin I converting enzyme inhibitor, captopril, inhibited significantly the drinking response, but not the increased urine output, accompanying administration of bethanechol (8 mg/kg). The effect of bethanechol and the beta-adrenergic agonist, isoproterenol (25 micrograms/kg) separately and in combination, on water intake was also studied. Both compounds increased water intake but they exerted no interactive effect when administered simultaneously. Administration of bethanechol (8 mg/kg) to conscious rats was also accompanied by a significant reduction in both mean blood pressure and heart rate that reached minimal levels within 10 min after treatment. Both responses had returned to control level by one hr after treatment. These results suggest that bethanechol induces drinking in rats by way of the renin-angiotensin system.

Animals↗
PubMed1982

Interrelationships among blood pressure, renal function, thyroid activity and renal thyroid depressing factor in renal hypertensive rats.

Renal hypertension in rats was accompanied by both a decrease in thyroid activity (i.e., decreased total serum triiodothyronine concentration, increased serum thyroid-stimulating hormone concentration and increased thyroid weight) and renal function (i.e., reduced renal concentrating ability, increased blood urea nitrogen and serum creatinine concentrations). Systolic blood pressure, thyroid activity and level of renal function of individual hypertensive rats correlated significantly with the content of a thyroid-depressing factor in their kidneys. The results suggest, but do not prove, that a factor released by the kidneys during elevation of blood pressure and/or reduction in renal function may reduce thyroid function in the rat.

Animals↗
PubMed1982

Effect of theophylline on thyroid status in the rat.

The effect of administration of theophylline, thyroxine (T4), or a combination of the two, for 14 days on body weight, food intake, serum concentrations of T4 and 3,5,3'-triiodothyronine (T3), and on the rate of 5'-monodieodination of T4 to T3 by hepatic and renal homogenates was evaluated. Administration of T4 (25 micrograms/kg b.w./day) increased the serum concentration of T4 and T4 5'-deiodinase activity. Administration of theophylline (191 mg/kg b.w./day) increased the serum concentration of theophylline to 28.5 micrograms/ml, increased food intake, but decreased both the concentration of T4 in serum and also T4 5'-deiodinase activity. Administration of a combination of T4 and theophylline returned T4 5'-deiodinase activity to control levels. Since the addition of only high concentrations of theophylline to incubation mixtures inhibited T4 5'-deiodinase directly, it is most likely that the effect of theophylline in vivo on the activity of the T4 5'-deiodinase enzyme is indirect and secondary to inhibition of thyroid hormone secretion.

Animals↗
PubMed1982

Thermogenic drinking: mediation by osmoreceptor and angiotensin II pathways.

Exposure of rats to air at 5 C for 1-12 days is accompanied by a relative dehydration in spite of the continued presence of water. Dehydration during exposure to cold was manifested by: 1) a reduction in the ratio of water/food ingested; 2) an increase in the ratio of urine excreted/water ingested; 3) an increased evaporative water loss; 4) an increased serum osmolality and chloride concentration; and 5) a striking thirst and ingestion of water after transfer from cold to air at 26 C. Drinking began within 15 min and lasted approximately 1 h. Thermogenic drinking persisted for at least 120 days of exposure to cold. It was not thwarted by preventing access to water for either 1 or 2 h after transfer to warm air, but either intragastric or intraperitoneal administration of a water load equal to 3% of body weight inhibited water intake after transfer. These characteristics of thermogenic drinking are similar to those observed after 24 h of dehydration at 26 C; they also suggest that the cold-exposed rat is dehydrated relative to controls. These results suggest that osmoreceptors may play a role in the induction of thermogenic drinking. However, angiotensin II receptors may also play a role. Thermogenic drinking was inhibited by a beta 2-adrenergic, but not a beta 1-adrenergic, antagonist as well as by captopril, an inhibitor of the conversion of angiotensin I to angiotensin II. Further, plasma renin activity increased fourfold within 15 min after removal from cold. This suggests that an additional component involved in thermogenic drinking is the angiotensin II receptor. The extent to which thermogenic drinking is mediated by each pathway is unknown and will require additional studies.

Adrenergic beta-Antagonists↗
PubMed1982

Edward F. Adolph.

Explore the source record for details and available documents.

History, 20th Century↗
PubMed1982

Effects of chronic treatment with thyroxine and estradiol on estrogen concentration in serum and on hepatic microsomal catechol estrogen formation in female rats.

The effects of chronic treatment with thyroxine (T4) and estradiol on hepatic microsomal metabolism of estrogens to catechol products were studied and the extent to which activity in vitro correlated with serum estradiol concentrations in vivo was assessed. Female rats were treated with either estradiol benzoate (EB; 56 micrograms/kg/day from silastic implants), T4 (50 micrograms/kg/day, s.c.) or combined EB + T4 for 35 days. Animals treated with EB + T4, but not T4 alone, showed a significant increase above controls both in the concentration of triiodothyronine in serum and food consumption. Serum concentrations of endogenous estradiol in untreated control and T4-treated animals were similar. Although both EB-treated groups received comparable doses of steroid from silastic implants, the concentration of estradiol in serum was 30% lower in EB + T4-treated animals than in animals treated with EB alone. Formation of catechol estrogen metabolites by hepatic microsomes was not significantly altered by EB and T4 administered separately, but enzyme activity was increased significantly with combined hormonal therapy. In contrast, microsomal hydroxylation of testosterone was not increased by treatment with EB + T4, data which suggest that total steroid hydroxylase activity was not enhanced by combined hormonal administration. Correlation analysis of microsomal catechol estrogen formation in vitro with serum concentrations of estradiol in vivo indicated related to the concentration of estrogen in serum only after coadministration of a low dose of T4 with EB.

Animals↗
PubMed1981

Normal excretion of m-hydroxymandelic acid in hypertensive patients.

o-Hydroxymandelic acid (OHMA), m-hydroxymandelic acid (MHMA) and p-hydroxymandelic acid (PHMA) were measured in the urine of 42 normotensive and 54 hypertensive patients. Patients having high urinary MHMA levels were all found to be ingesting medications containing m-synephrine (phenylephrine). These patients also had high levels of urinary m-synephrine which was excreted as the glucuronide. When patients ingesting m-synephrine were excluded from the analysis, no significant differences were observed between the two groups for the urinary excretion of OHMA, MHMA and PHMA.

Adolescent↗
PubMed1981

Peripheral conversion of L-5-hydroxytryptophan to serotonin induces drinking in rats.

Female rats administered serotonin (0.25 to 4.0 mg/kg, s.c.) showed a dose-dependent increase in water intake. The dipsogenic response was nearly maximal when 2 mg/lg was administered s.c. and plateaued by 2 hr after treatment. l-5-Hydroxytryptophan (5-HTP), the precursor of serotonin, is also a potent dipsogen which induces drinking by way of the renin-angiotensin system. The possibility that the dipsogenic activity of 5-HTP is dependent on decarboxylation to serotonin was the objective of these studies. Either benserazide (30 mg/kg. s.c.), a central and peripheral decarboxylase inhibitor, or carbidopa (6.5 mg/kg, s.c.), a peripheral decarboxylase inhibitor, was administered 15 min prior to the dipsogen. Both decarboxylase inhibitors attenuated the dipsogenic response to 5-HTP (25 mg/kg, s.c.) but not to serotonin (2 mg/kg, s.c.). The peripheral serotonergic receptor antagonist, methysergide (3 mg/kg, i.p.), blocked the dipsogenic responses to both 5-HTP (25 mg/kg, s.c.) and serotonin (2 mg/kg, s.c.). There was no interaction between 5-HTP (18 mg/kg, s.c.) and serotonin (1 mg/kg, s.c.) when administered simultaneously with respect to their dipsogenic effects. Thus, the drinking response accompanying administration of 5-HTP occurs following peripheral conversion to serotonin which, in turn, activates peripheral serotonergic receptors. The mechanisms(s) by which activation of peripheral serotonergic receptors increases water intake is not known, but appears to involve release of renin from the kidney.

5-Hydroxytryptophan↗
PubMed1981

Effects of serotonin and L-5-hydroxytryptophan on plasma renin activity in rats.

The effects of dipsogenic doses of l-5-hydroxytryptophan (5-HTP) and serotonin on plasma renin activity (PRA), blood pressure, and body temperature were determined in unanesthetized female rats. Both serotonin (2 mg/kg, s.c.) and 5-HTP (25 mg/kg, s.c.) induced six-fold increases in PRA measured 1 hr after drug administration. The central and peripheral decarboxylase inhibitor, benserazide (30 mg/kg, s.c.), as well as the peripheral decarboxylase inhibitor, carbidopa (6.5 mg/kg s.c.), prevented the increase in PRA associated with administration of 5-HTP. This suggests that 5-HTP must be converted to serotonin peripherally to increase PRA. At the doses used, serotonin decreased mean blood pressure and colonic temperature of unanesthetized rats while 5-HTP was without effect. The increase in PRA induced by 5-HTP does not appear, therefore, to be a response to either hypotension or a decrease in colonic temperature. Since 5-HTP must be converted to serotonin to initiate both a drinking response and an increase in PRA, the results suggest that the decrease in blood pressure and colonic temperature following administration of serotonin may not be important in induction of the drinking response and the increase in PRA. The mechanism by which activation of the renin-angiotensin system occurs following peripheral administration of either 5-HTP or serotonin remains for further study.

5-Hydroxytryptophan↗
PubMed1981

L-5-Hydroxytryptophan-induced drinking in rats: possible mechanisms for induction.

Administration of L-5-hydroxytryptophan (25 mg/kg body weight, SC) to female rats resulted in copious drinking. The dipsogenic response to administration of L-5-hydroxytryptophan (5-HTP) was blocked by propranolol (6 mg/kg body weight, IP), a beta-adrenergic antagonist, and captopril (35 mg/kg body weight, IP), an angiotensin converting enzyme inhibitor. In addition, clonidine (12.5 and 25 microgram/kg body weight, IP), a central alpha-adrenergic agonist known to inhibit renin release, attenuated drinking during 1, 2 and 3 hours after 5-HTP was administered. These results suggest that 5-HTP-induced drinking is mediated by way of the renin-angiotensin system. Haloperidol (150 microgram/kg body weight, IP), a dopaminergic antagonist, also attenuated the dipsogenic response to administration of 5-HTP. In addition, incremental reductions in 5-HTP-induced drinking with increasing doses of spiperone (37.5 to 150 microgram/kg body weight, IP), a more potent dopaminergic antagonist, were demonstrated. Thus, the dipsogenic response to administration of 5-HTP to rats is dependent on both the renin-angiotensin system and an intact dopaminergic pathway.

5-Hydroxytryptophan↗
PubMed1981

Antidipsogenic effect of clonidine on angiotensin II-, hypertonic saline-, pilocarpine- and dehydration-induced water intakes.

The dipsogenic responses of female rats to administration of angiotensin II (150 micrograms/kg b.w., IP), pilocarpine (3 mg/kg IP), hypertonic saline (1 M NaCl solution, 1% b.w.), and a 24 hour dehydration were attenuated by acute IP administration of graded doses of the central and peripheral alpha 2-adrenergic agonist, clonidine. For all treatments except dehydration, clonidine inhibited significantly the dipsogenic response at the lowest dose used (6 micrograms/kg, IP). The first significant effect on dehydration-induced drinking required approximately a 4 fold higher dose (25 micrograms/kg, IP). Attenuation of the response to these dipsogenic stimuli by clonidine, suggests that its ability to stimulate alpha-adrenergic receptors centrally may play an important role in its dipsogenic inhibitory activity.

Angiotensin II↗
PubMed1981

Thermoregulatory responses of tailed and tailless rats to isoproterenol.

Colonic temperatures were measured in tailed and tailless rats at an ambient temperature (Ta) of 26 degrees C prior to and following administration of isoproterenol, a beta-adrenergic agonist, at doses of 0, 12.5, 25.0, 50.0, and 100.0 micrograms.kg-1. There was no significant difference between the colonic temperatures of tailed and tailless rats before drug injection. However, mean colonic temperature of tailless rats increased to a maximal level approximately 0.3 degrees higher than that of tailed rats after injection of 25.0, 50.0, and 100.0 micrograms isoproterenol per kilogram. The duration of the hyperthermic response was 50-60 min longer in tailless than tailed rats after administration of 50 and 100 micrograms isoproterenol per kilogram. The rate of oxygen consumption (heat production) increased by 4.5 mL.min-1.kg-0.75 in both tailed and tailless rats after administration of 50 micrograms isoproterenol per kilogram, the only dose tested. Mean colonic temperature of tailless rats was significantly higher, by 0.2-0.5 degrees than that of tailed rats during the initial 60 min of exposure to Ta 36 degrees C and during the first 40 min following removal from Ta 40 degrees C to Ta 28 degrees C. These results suggest that the tail of the rat is required for short-term maintenance of colonic temperature during both external and internal heat stresses.

Animals↗