Biomedical subjects

M J Fregly

Publications and source records attributed to M J Fregly.

At least 73 records · Page 4Linked to original sources

PubMed1991

Reduction in the elevated blood pressure of Dahl salt-sensitive rats treated chronically with L-5-hydroxytryptophan.

Rats of the Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) strains were placed on a 4% NaCl diet and blood pressures were monitored. Chronic subcutaneous infusion L-5-hydroxytryptophan (L-5-HTP, 12.6 mg/day) by osmotic minipumps significantly decreased the elevated systolic blood pressure of DS rats on a 4% NaCl diet. Blood pressures of DR rats were unaffected by treatment with L-5-HTP. Cardiac hypertrophy was associated with Dahl salt-induced hypertension. However, treatment with L-5-HTP failed to reduce the weight of the heart significantly. These results suggest that chronic administration of L-5-HTP was effective in reducing the elevated blood pressure in the DS model. The specific mechanisms by which L-5-HTP reduces the elevated blood pressure in DS rats is not clear and remains for further study.

5-Hydroxytryptophan↗

PubMed1991

Effect of chronic dietary treatment with L-tryptophan on the development of cold-induced hypertension in rats.

This study was designed to assess the effect of chronic dietary administration (2.5 and 5.0% by weight) of the neutral amino acid, L-tryptophan, on the development of hypertension during chronic exposure to cold. In addition, a warm-adapted and cold-treated control group receiving unsupplemented food were used. Chronic administration of the lower dose of L-tryptophan (850 mg/day) prevented the elevation of blood pressure attenuated cardiac hypertrophy, and had no effect on body weight during exposure to cold. The higher dose of L-tryptophan (1,690 mg/day) attenuated the rate of blood pressure increase, did not affect cardiac hypertrophy, attenuated the gain in body weight, and increased the urinary output of epinephrine. Thus, this dose may be associated with some toxicity. Both doses of tryptophan failed to prevent certain other responses characteristically occurring during exposure to cold: i.e. increased weight of the kidneys, adrenal glands and brown adipose tissue; increased food and water consumption; increased dipsogenic responsiveness to angiotensin II, and increased plasma aldosterone concentration. The results indicate that chronic dietary administration of L-tryptophan (850 mg/day) can prevent the development of cold-induced hypertension, as it can in all other models of hypertension tested thus far in rats.

Aldosterone↗

PubMed1991

Effect of chronic treatment with clonidine and spironolactone on cold-induced elevation of blood pressure.

The present study was designed to determine whether antihypertensive agents known to affect the renin-angiotensin-aldosterone (RAA) system might affect the elevation of blood pressure induced by chronic exposure to cold. Spironolactone, a mineralocorticoid receptor blocker, was added to the food and administered to rats chronically exposed to cold. In addition, clonidine, and alpha 2-adrenergic agonist and inhibitor of renin secretion, was administered to another group of cold-exposed rats by daily intraperitoneal injection. A warm-adapted and a cold-treated control group were also used. Chronic administration of spironolactone prevented the development of hypertension but failed to prevent other adaptive physiological changes characteristically occurring during exposure to cold and seen in the cold-treated control rats. Thus, increased weight of the heart, kidneys, adrenals and brown adipose tissue, increased dipsogenic responsiveness to angiotensin II, increased urinary outputs of norepinephrine and epinephrine, and increased food and water consumption were observed in all rats, treated and untreated, during exposure to cold. Similarly, daily injection of clonidine attenuated the elevation of blood pressure but also failed to prevent the other adaptive physiological changes characteristic of cold. These results are consistent with the hypothesis that the RAA system plays a role in the development of the cold-induced elevation of blood pressure.

Aldosterone↗

PubMed1991

Prevention of cold-induced increase in blood pressure of rats by captopril.

To assess the possibility that the renin-angiotensin system may play a role in the development of cold-induced hypertension, three groups of rats were used. Two groups were exposed to cold (5 +/- 2 degrees C) while the remaining group was kept at 26 +/- 2 degrees C. One group of cold-treated rats received food into which captopril (0.06% by weight) had been thoroughly mixed. The remaining two groups received the same food but without captopril. Systolic blood pressure of the untreated, cold-exposed group increased significantly above that of the warm-adapted, control group within 4 weeks of exposure to cold. In contrast, chronic treatment with captopril prevented the elevation of blood pressure. Rats were killed after 4 months of exposure to cold. At death, the heart, kidneys, adrenal glands, and interscapular brown fat pad were removed and weighed. Although captopril prevented the elevation of blood pressure in cold-treated rats, it did not prevent hypertrophy of the kidneys, heart, and interstitial brown adipose tissue that characteristically accompanies exposure to cold. Thus, chronic treatment with captopril prevented the elevation of blood pressure when administered at the time exposure to cold was initiated. It also reduced the elevated blood pressure of cold-treated rats when administered after blood pressure became elevated. This suggests that the renin-angiotensin system may play a role in the elevation of blood pressure during exposure to cold.

Animals↗

PubMed1990

Thirst and sodium appetite in Dahl rats.

In confirmation of a previous study, rats of the Dahl S and R sublines exhibited no spontaneous preference for dilute NaCl solutions and an aversion for isotonic and hypertonic NaCl solutions when they were offered in a 2-bottle choice with water. A hysteresis effect was observed when choice was offered between water and a descending series of concentrations of NaCl solution compared with a preceding increasing series. In response to either chronic dietary administration of an angiotensin I converting enzyme inhibitor (ACEI) or acute sodium depletion, rats of the R subline developed a strong NaCl appetite, but the S subline did not. In contrast, rats of both sublines showed an NaCl appetite in response to a regimen of deoxycorticosterone acetate (DOCA). In acute drinking tests, rats of the S subline drank less water than those of the R subline in response to administration of either isoproterenol, ACEIs, or hypovolemia. Both R and S sublines drank similar amounts of water after SC administration of angiotensins I and II, and hypertonic NaCl. Compared with R rats, S rats had lower plasma renin activity in several of the above conditions, and their decreased thirst and sodium appetite appears to be a direct result of an underactive renin-angiotensin system.

Animals↗

PubMed1990

Comparison of the dipsogenic responsiveness of Long-Evans and Sprague-Dawley rats.

The dipsogenic responsiveness of the Sprague-Dawley (albino) and Long-Evans (hooded) strains of rats was compared. The responsiveness of the angiotensin II pathway for induction of drinking was assessed by means of acute administration of the beta-adrenoceptor agonist, isoproterenol (25 micrograms/kg, SC), angiotensin I (150 micrograms/kg, SC), and angiotensin II (150 micrograms/kg, SC). The results show that rats of the Long-Evans (hooded) strain drink less water than those of the Sprague-Dawley strain in response to acute administration of either isoproterenol or angiotensin I. However, there was no difference between groups in water intake resulting from administration of angiotensin II. This suggests that the Long-Evans strain has less capacity to convert angiotensin I to angiotensin II than the Sprague-Dawley strain, but that responsiveness of the Long-Evans strain to angiotensin II is similar to that of the Sprague-Dawley strain. The responsiveness of the osmoreceptor pathway for induction of drinking was also assessed both by measurement of the drinking response to acute administration of hypertonic saline (1% body weight of 1 M NaCl solution, IP) and a 24-hour dehydration. The results show that rats of the Long-Evans strain drink less water in response either to administration of hypertonic saline or to dehydration than those of the Sprague-Dawley strain. This suggests that responsiveness to stimulation of the osmoreceptor pathway of the Long-Evans strain induces less drinking than in the Sprague-Dawley.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

PubMed1990

Reversibility of cold-induced hypertension after removal of rats from cold.

Chronic exposure of rats to cold air induces hypertension, including elevation of blood pressure and cardiac hypertrophy. The present study was designed to assess reversibility of these changes after removal from cold. Five groups of six male rats each were exposed to cold (5 +/- 2 degrees C) for 39 days, while six control rats were maintained at 26 +/- 2 degrees C. Systolic blood pressures of the rats in one of the cold-treated groups, as well as the controls, were measured twice weekly throughout the experiment. Blood pressure of the cold-exposed rats (150 +/- 3 mmHg; 1 mmHg = 133.3 Pa) became elevated significantly above that of controls (129 +/- 3 mmHg) within 4 weeks. On day 39 of cold exposure, one group (six rats) of the cold-treated rats was sacrificed while still in the cold. The remaining four groups of cold-treated rats were than removed from cold and kept at 26 +/- 2 degrees C. One group of cold-treated rats was sacrificed weekly thereafter. During the last week, the six control rats were also sacrificed. At death, the heart, kidneys, and adrenal glands were removed and weighed. Mean heart weight of the cold-treated group (346 +/- 7 mg/100 g body weight), sacrificed prior to removal from cold, was significantly (p less than 0.01) greater than that of controls (268 +/- 5 mg/100 g body weight). The increased heart weight of the cold-treated group appeared to result mainly from an increase in left ventricular weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Factors affecting cold-induced hypertension in rats.

A 3- to 4-week exposure of rats to a cold environment (5 +/- 2 degrees C) induces hypertension, including elevation of systolic, diastolic, and mean blood pressures and cardiac (left ventricular) hypertrophy. The studies described here were designed to investigate some factors affecting both the magnitude and the time course for development of cold-induced hypertension. The objective of the first study was to determine whether there was an ambient temperature at which the cold-induced elevation of blood pressure did not occur. The objective of the second experiment was to determine whether body weight at the time of exposure to cold affected the magnitude and time course for development of hypertension. To assess the first objective, male rats were housed in a chamber whose temperature was maintained at 5 +/- 2 degrees C while others were housed in an identical chamber at 9 +/- 2 degrees C. After 7 days of exposure to cold, the rats exposed to the colder temperature had a significant elevation of blood pressure (140 +/- 2 mm Hg) compared with the group maintained at 9 degrees C (122 +/- 3 mm Hg). The rats exposed to 9 degrees C had no significant elevation of systolic blood pressure at either 27 or 40 days after initiation of exposure to cold. At the latter time, the temperature in the second chamber was reduced to 5 +/- 2 degrees C. By the 25th day of exposure to this ambient temperature, the rats had a significant increase in systolic blood pressure above their levels at 9 degrees C. Thus, there appears to be a threshold ambient temperature for elevation of blood pressure during exposure to cold. That temperature appears to lie somewhere between 5 and 9 degrees C. The second objective was assessed by placing rats varying in weight from approximately 250 to 430 g in air at 5 degrees C. There was a highly significant direct relationship (r = 0.96) between body weight at the time of introduction to cold and the number of days required to increase systolic blood pressure by 10 mm Hg above pre-cold exposure level. The third objective was to make an initial assessment of potential differences among strains of rats with respect to development of cold-induced hypertension. To this end, rats of the Fischer 344 strain were used. Systolic blood pressures of these rats also increased during chronic exposure to cold.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Some characteristics of post-hypoxia-induced drinking in rats.

When rats are returned to a normoxic environment after chronic exposure to hypoxia, they manifest a striking drinking response. Earlier studies had shown that the drinking response was an inverse linear function of the percentage of oxygen in the air to which the rats had been exposed. An objective of the present experiment was to measure the post-hypoxic drinking response at intervals during a 71-d exposure to an atmosphere containing 12% oxygen in nitrogen to assess whether the response could be observed throughout this entire period. The results suggest that the response continued unabated throughout the duration of exposure to hypoxia. The mechanism(s) accounting for the posthypoxic drinking response cannot be stated with certainty. However, the results of these studies indicate that administration of the betra-adrenoceptor antagonist, propranolol (6 mg/kg, i.p.), failed to affect the magnitude of the drink following return from hypoxia to normoxia. Hence, it is unlikely that the posthypoxic drinking response is mediated by an increase in beta-adrenergic activity.

Adaptation, Physiological↗

PubMed1989

Preference threshold for NaCl solutions and sodium homeostasis in hypophysectomized rats.

The NaCl preference threshold concentrations of male hypophysectomized (hypox) and intact rats were determined using a two-bottle choice paradigm. Although hypox rats ingested more total fluid daily (ml/100 g body weight), including water and NaCl solution, than intact rats, there were no significant differences between groups in either preference threshold (8.0 mEq/l) or preference maximum (90 mEq/l) concentrations. Further, the ratio of NaCl to total fluid ingested did not differ between hypox and intact groups throughout the large range of concentrations of NaCl solution presented to them. To assess their ability to conserve sodium, both intact and hypox rats were maintained on a sodium-deficient diet and distilled water for 3 days. Both groups reduced their urinary sodium outputs significantly compared to counterparts maintained on a sodium-replete diet. This suggests that the functional integrity of the renin-angiotensin-aldosterone system was maintained in the hypox rats. Resting plasma aldosterone concentrations, measured at the end of the experiment, did not differ significantly between groups. Assessment of completeness of hypophysectomy was made by measurement of daily urinary excretion of epinephrine and by change in body weight during the course of the experiment. Daily urinary excretion of epinephrine by hypox rats was reduced to one-tenth that of intact controls. Hypox rats also failed to grow during the course of the experiment. By application of both of these criteria, the rats were completely hypophysectomized.

Aldosterone↗

PubMed1989

Effect of chronic dietary treatment with 1-tryptophan on spontaneous salt appetite of rats.

Chronic dietary treatment with 1-tryptophan (2.5 and 5.0% in food) reduced the exaggerated spontaneous NaCl intake induced by deoxycorticosterone acetate (DOCA) in rats. In the absence of DOCA, chronic (4-week) dietary treatment with 1-tryptophan (5.0% in food) failed to affect significantly spontaneous NaCl intake. In addition, treatment with tryptophan in the absence of DOCA failed to affect significantly systolic blood pressure, plasma renin activity, plasma aldosterone concentration, and the weights of the heart, kidneys, adrenals, and thyroid gland. It also failed to affect the specific binding of [125I]-Ang II to neuronal membranes isolated from the diencephalon of the rats. However, the contents of both serotonin and 5-hydroxyindoleacetic acid in the lower brain stem were increased significantly by chronic treatment with tryptophan. These results suggest that the effect of chronic treatment with tryptophan to reduce the salt appetite of DOCA-treated rats is a specific effect of this amino acid under these conditions and may be related to the ability of tryptophan to prevent the upregulation of specific Ang II receptors induced by DOCA.

Angiotensin II↗

PubMed1989

Activity of the hypothalamic-pituitary-thyroid axis during exposure to cold.

It seems clear from the studies reviewed here that there is adequate evidence to support the concept of a biphasic response of the thyroid gland to cold as first postulated by Moll et al. (1972). The initial response to acute exposure to cold begins at the level of the hypothalamus as a result of either neural stimuli from skin and other areas and/or blood of somewhat lower than normal temperature reaching the hypothalamus (Andersson et al., 1963). As a result, the secretion of norepinephrine and/or dopamine may increase, and serotonin and/or somatostatin may decrease. The net result of these is an increase in the release of TRH from the hypothalamus. This, in turn, stimulates the cascade for the release of TSH from the anterior pituitary gland and thyroid hormone from the thyroid gland. Moll et al. (1972) postulated the lack of a feedback limb in this acute phase, and, indeed, this may be the case. It is possible, however, that certain hormones, such as somatostatin, norepinephrine, T3, and T4 could act in the capacity of feedback inhibitors. Additional experiments will be required to assess this possibility. The transitional link between the acute (less than 1 day) and chronic (greater than 1 day) phases of the response of the thyroid gland to cold could be T4 itself. An increase in the concentration of T4 in plasma has been reported to increase peripheral deiodination of T4 to T3 by kidneys and liver of rats. There are no studies at present to indicate that hepatic conjugation can be increased by elevation of plasma levels of T4 and T3. If it can, these responses would provide adequate reasons as to why peripheral metabolism of thyroid hormones increases during chronic exposure to cold. The time-course for these changes to occur needs to be studied in greater detail to establish the sequence of events following acute exposure to cold. The latter may also increase urinary excretion of T4 and T3 in man, but not the rat. This suggests that another aspect of exposure to cold needing additional study is measurement of the binding affinities of T4 and T3 for their transport proteins during exposure to cold as compared to affinities prior to exposure to cold. If binding affinities are reduced, the amount of free hormones would increase and, consequently the likelihood of being excreted into urine and conjugated by the liver would also increase.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Effect of chronic dietary treatment with L-tryptophan on the maintenance of hypertension in spontaneously hypertensive rats.

Chronic dietary administration of L-tryptophan at 2.5 and 5.0% by weight reduced the elevated systolic blood pressure of spontaneously hypertensive (SH) rats. Blood pressure was reduced significantly by 3 weeks after initiation of treatment and continued to fall during the course of the 15 weeks of treatment. Body weights of the treated rats were not affected significantly by treatment, nor were daily food and fluid intakes and urine outputs. SH rats, treated with the higher dose of tryptophan, also significantly reduced their urinary outputs of epinephrine and norepinephrine compared with SH controls, while both doses of tryptophan increased urinary outputs of dopamine significantly above that of SH controls. Treatment with tryptophan increased significantly the specific binding of [125I]angiotensin II (Ang II) to membranes from the diencephalon in a dose-dependent manner. Measurement of catecholamine concentration of the supernatant from homogenates used for the Ang II binding assay revealed a significant correlation between the specific binding of Ang II to brain membranes of the two tryptophan-treated groups and the concentration of norepinephrine in the supernatant. There was also a significant correlation between the specific binding of Ang II and the concentration of dopamine in the supernatant of the control group and the group treated with the higher dose of tryptophan. These results show that chronic dietary administration of tryptophan can reduce the elevated blood pressure of SH rats and support the possibility that this neutral amino acid may act via its effect on the concentration of the neurohormones, norepinephrine and dopamine, in the diencephalon to regulate the binding of Ang II to its receptors.

Angiotensin II↗

PubMed1989

Modulation of angiotensin II binding sites in neuronal cultures by mineralocorticoids.

Previous studies have determined that mineralocorticoid hormones are able to increase the number of angiotensin II (ANG II)-specific binding sites in rat diencephalon and in neuronal cultures and also increase the drinking response elicited by centrally injected ANG II. In the present study, we have examined the specificity and mechanisms of this mineralocorticoid action. In neuronal cultures from the hypothalamus and brain stem (H/BS), both D-aldosterone and deoxycorticosterone acetate (DOCA) caused significant time- and dose-dependent increases in 125I-labeled ANG II-specific binding. This effect was not mimicked by the synthetic glucocorticoid dexamethasone, or by testosterone, beta-estradiol or progesterone. However, the steroid corticosterone induced a moderate increase in [125I] ANG II binding. This may have occurred as a result of its high affinity for the mineralocorticoid type I receptor. DOCA was ineffective in increasing [125I]ANG II specific binding both in neuronal cultures prepared from the cerebellum and in pure astrocytic glial cultures, indicating that this mineralocorticoid effect is specific both for neurons and for certain brain regions. The increase in [125I]ANG II-specific binding elicited by DOCA was abolished by cotreatment with the mineralocorticoid receptor blockers mespirenone or ZK97894 and by cotreatment with cycloheximide. Taken together, these observations suggest that the mineralocorticoid-induced increase in [125I]ANG II-specific binding in H/BS neuronal cultures is a specific event, which is mediated via mineralocorticoid type I receptors and which requires protein synthesis.

Aldosterone↗

PubMed1989

Development of hypertension in rats during chronic exposure to cold.

Resting systolic, diastolic, and mean blood pressures (MBP), as well as heart rates, of unanesthetized, unrestrained, cold-acclimated (CA, 4 wk, 6 degrees C) rats were measured by direct arterial cannula and compared with those of controls maintained at 25 degrees C. Exposure to cold increased all these measurements significantly. Mean heart weight of CA rats was also increased significantly above that of controls. The responsiveness of MBP and heart rate to administration of the beta-adrenergic agonist, isoproterenol (3, 5, and 8 micrograms/kg ip), to unanesthetized, unrestrained, CA rats during exposure to air at 6 degrees C was similar to, and possibly less than, that of warm-acclimated (WA) rats measured at 25 degrees C. Acute administration of the alpha-adrenergic agonist, phenylephrine (100 micrograms/kg ip), to CA rats while in air at 6 degrees C induced less of a change in MBP from pretreatment level than was observed in WA rats. However, no differences were observed between groups when changes in heart rate from pretreatment level were compared. A similar statement may be made for a higher dose of phenylephrine (150 micrograms/kg ip), although MBP were elevated to higher levels in both groups with the higher dose. Abrupt exposure of WA rats to cold (6 degrees C) resulted in a sharp increase in heart rate and a more gradual increase in MBP over a period of 1 h. Removal of CA rats from 6 to 25 degrees C resulted in a gradual decrease in heart rate with no significant change in MBP during the ensuing hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

PubMed1989

Effect of domperidone on renal response to certain atrial natriuretic substances in rats.

Anesthetized rats, maintained on an intravenous (1 ml/h) infusion of saline, were injected with either atrial extract from normal rats (AE), atriopeptin III (APIII, 24 amino acids) or atrial peptide (AP, 28 amino acids) as either a bolus injection (1 atrial equivalent of AE, 1 microgram APIII, or 1 microgram AP) or by constant infusion (1.7 ng APIII or AP/min for 30 min) in isotonic saline. Diuretic, natriuretic, and kaliuretic responses were determined by subtraction of baseline values from the renal response during the first 15 min after administration of the atrial natriuretic factor (ANF). The change in renal response observed in rats receiving saline and a bolus injection of an ANF was compared to the change in response observed in the same rats that received the dopaminergic antagonist, domperidone (0.2 microgram/kg, i.v.), and the same ANF. In the case of the renal response following infusion of an ANF, a paired comparison was made between domperidone-treated and untreated rats. Domperidone attenuated the renal response to AP, administered either as a bolus injection or a constant infusion, whereas domperidone significantly reduced renal response to APIII only following constant infusion. The renal response to a bolus injection of AE was not affected by the administration of domperidone. These findings suggest that the renal action of the putative circulating form of ANF, i.e. AP, is mediated via dopaminergic receptors, and that the route of administration may affect the mechanism of action of an ANF.

Animals↗

PubMed1988

Behavioral and physiological aspects of body fluid homeostasis in Fischer 344 rats.

Previous studies have shown that Fischer 344 rats, unlike many other strains, have neither a spontaneous preference for dilute NaCl solutions nor an excessive consumption of it after sodium depletion. The present studies examine some characteristics of water intake in Fischer 344 rats. Their spontaneous water intake was only about 50% of that of age-matched Sprague-Dawley rats, and the water-to-food ratio was about 30% lower. When water was added to the food, Fischer 344 rats decreased their fluid intake by a corresponding amount, whereas Sprague-Dawley rats continued to drink substantial amounts. In the absence of food, Fischer 344 rats reduced their water intake by a greater fraction than rats of the Sprague-Dawley strain. Physiological changes during these studies were as expected from the behavioral data, except that plasma protein concentration was consistently 10% higher in Fischer 344 rats. In contrast to this economy in their spontaneous drinking, water intakes of Fischer 344 rats were comparable to Sprague-Dawley rats in response to water deprivation, and administration of either hypertonic NaCl or angiotensin II, and in a sham-drinking paradigm. However, following treatment with either isoproterenol or polyethylene glycol, Fischer 344 rats drank considerably less than Sprague-Dawley rats. Possible reasons for, and implications of, these strain differences in drinking are discussed.

Animals↗

PubMed1988

Regulation of intakes of water and NaCl solutions in Fischer 344 rats: contrasts and comparisons between strains.

We present an overview of the differences in intakes of both water and NaCl between different strains of rat, with emphasis on Fischer 344 (F344) and Sprague-Dawley (SD) strains. Relative to SD, rats of the F344 strain show less spontaneous or secondary drinking both with food present and during food deprivation. The water intake of rats of the F344 strain is strongly inhibited when water is added to their food, but rats of the SD strain show less inhibition and consume excessive amounts of fluid. In studies of primary drinking, induced by treatment with various dipsogens, rats of the F344 strain consumed water in amounts that were generally comparable to those expected from rats of the SD strain, with the exception of reduced intakes in response to either polyethylene glycol-induced hypovolemia or treatment with isoproterenol. The hematocrit ratio, resting plasma renin activity and directly-measured plasma protein concentrations were similar between F344 and SD strains. We also review findings that rats of the F344 strain show no spontaneous preference for dilute NaCl solutions, and show that both a strong preference and a low preference threshold are induced by chronic treatment with ramipril. Other manipulations that induce an appetite for NaCl in the F344 strain are summarized.

Angiotensin II↗