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M J Fregly

Publications and source records attributed to M J Fregly.

At least 55 records · Page 3Linked to original sources
PubMed1992

Comparison of preference thresholds for NaCl solution in rats of the Sprague-Dawley and Long-Evans strains.

Rats of the Sprague-Dawley and Long-Evans strains were compared with respect to their preference threshold and preference maximum concentrations for NaCl solution in a two-bottle choice paradigm. The preference threshold for NaCl in rats of the Sprague-Dawley strain occurred when the concentration of NaCl presented was 0.030 M. The preference maximum concentration was 0.10 M. In the case of rats of the Long-Evans strain, a preference threshold concentration was not clearly manifested although the preference maximum concentration was also 0.10 M. Thus, the previously reported lack of an appetite for isotonic NaCl solution in rats of the Long-Evans strain compared to those of the Sprague-Dawley strain is most likely related to the failure of rats of the former strain to discriminate between water and NaCl solution until the concentration of NaCl exceeds 0.15 M. However, at this concentration, both strains rejected NaCl solution in favor of water. In contrast to the results with NaCl solution, rats of the Long-Evans strain appear to have a greater appetite for 5% glucose solution than do those of the Sprague-Dawley strain. Whether this is related to a reduced preference threshold concentration for glucose remains to be tested.

Animals↗
PubMed1992

Hyperhydrating effect of acute administration of angiotensin II in rats.

Water intake, urine output, and fluid exchange (water intake less urine output) were measured in rats at hourly intervals for 7 hours and at 24 hours following acute administration of angiotensin II (AII, 200 micrograms/kg SC). AII induced the expected abrupt increase in water intake and a more gradual increase in urine output. The change in fluid exchange (fluid exchange of the AII-treated group less fluid exchange of controls) became positive within the first hour after treatment with AII, decreased linearly with time, and reached 0 at approximately 10 to 12 hours after treatment with AII. When AII was administered intracerebroventricularly (50 ng), similar results were observed. In this case, the change in fluid exchange (delta F) reached 0 in about 6 hours. Imposition of a water load (1% of body weight, IP) on the group receiving AII SC failed to affect the time required for delta F to reach 0 if the water load was disregarded. However, inclusion of the load as a part of intake extended the time the rats remained in positive fluid balance beyond that of the nonloaded, AII-treated control group. In the case of the larger water load (3% of body weight, IP), delta F returned to that of controls in about 4 to 5 hours if the water load was disregarded. However, inclusion of the load as part of intake extended the period of hyperhydration well beyond that of both the nonloaded, AII-treated group and the AII-treated group given the 1% load.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Comparison of the hyperhydrating effects of angiotensin II and isoproterenol.

Administration of a single dose of angiotensin II (AII) has been shown to induce a state of hyperhydration in rats that can last from 6-10 h depending upon the route of administration and the dose. The objective of the present study was to determine whether another dipsogenic agent, isoproterenol (ISO), a beta-adrenoceptor agonist, could also induce a state of hyperhydration. The results indicate that a single SC dose of ISO can induce a hyperhydration that lasts from 4-6 h depending upon the dose administered. Administration of graded doses of either AII or ISO induced graded increases both in the time of hyperhydration and change in accumulative mean fluid exchange, (delta FE, fluid exchange of treated less fluid exchange of control). These two parameters were related linearly and directly for each drug, although the slopes, but not the intercepts, of the relationship for each drug differed significantly. Because the objective of optimal hyperhydration should be to achieve the longest duration of positive fluid balance with the least amount of ingested fluid (i.e., delta FE), the slopes of the two lines provide a convenient way to compare the hyperhydration induced by AII and ISO. By this criterion, it would appear that AII provides a more optimal hyperhydration than ISO.

Adrenergic beta-Antagonists↗
PubMed1992

Effect of losartan potassium and deoxycorticosterone acetate on tail skin temperature response to acute administration of angiotensin II.

The potent vasoconstrictor peptide, angiotensin II (AII) (200 micrograms/kg, SC), increases tail skin temperature (TST) and tail blood flow when acutely administered either peripherally (SC) or centrally (ICV) to rats. Colonic temperature declines with the increase in TST. These responses are apparently mediated by way of AII subtype receptor AT1 because they are blocked by acute administration of the nonpeptide AT1 receptor antagonist, losartan potassium (DuP 753) (10 mg/kg, SC). The responses were also blocked by the peptide AII receptor antagonist, saralasin, at 100 micrograms/kg SC. Chronic administration of the steroid deoxycorticosterone acetate (DOCA, 250-300 micrograms/day for 45 days) sensitized the response of TST to acute administration of AII. The increase in responsiveness resulting from chronic treatment with DOCA is consistent with the increase in dipsogenic responsiveness to AII under similar conditions. The latter was shown to be correlated with the upregulation of AII receptors in the diencephalon. While the location of the AII receptors mediating the increase in TST is not known with certainty, it is reasonable to suggest that they are also upregulated by chronic treatment with DOCA.

Angiotensin II↗
PubMed1992

The effect of intermittent exposure to cold on the development of hypertension in the rat.

Continuous exposure to a cold (5 degrees C) environment has been shown to induce hypertension in rats. The total time required for the first significant elevation of blood pressure is dependent on a number of factors, including the ambient temperature and the weight of the rat at the time of exposure to cold. The present study was also concerned with the minimal time of daily exposure to cold that would result in a significant elevation of blood pressure. To achieve this, we used four groups of rats. One was exposed to cold for 4 h daily (09:00 to 13:00), a second group was exposed to cold for 8 h daily (09:00 to 17:00), and a third was exposed for 24 h daily. The fourth group remained at 25 degrees C. Systolic blood pressures of the group exposed to continuous cold became elevated significantly above pre-cold exposure level within 2 weeks of cold exposure. Blood pressures of the groups exposed to cold for 4 and 8 h daily became elevated significantly above the level of the warm-adapted control group by day 27 of exposure to cold, but failed to reach the level of the chronically cold-exposed group even after 42 days of exposure to cold. There was a sigmoid-type relationship between the hours per day exposed to cold and systolic blood pressure at the end of the experiment. Thus, graded elevations of systolic blood pressure occur with increasing daily duration of exposure to cold.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Hypertension during chronic exposure to cold: comparison between Sprague-Dawley and Long-Evans strains.

It is now well established that chronic exposure of rats to cold (5-6 degrees C) induces an elevation of systolic, diastolic, and mean blood pressures and cardiac hypertrophy within 3 weeks. Since rats of the Long-Evans (LE) strain are known to be resistant to the induction of deoxycorticosterone salt induced hypertension, their cardiovascular responses to chronic exposure to cold were compared with those of rats of the Sprague-Dawley (SD) strain. The results of these studies revealed clear differences between the LE and SD strains of rats. Thus, rats of the SD strain had a significant elevation in their blood pressure; a significantly increased urinary output of norepinephrine and epinephrine; a significantly greater dipsogenic responsiveness to acute administration of angiotensin II, and significant increases in weights of the heart, kidneys, adrenals, and brown adipose tissue compared with their warm-adapted controls. All of these changes are characteristic of rats acclimated to cold. In contrast, rats of the LE strain appear to be less responsive to cold in that blood pressure failed to rise as sharply and to attain as high a level. Furthermore, urinary outputs of norepinephrine and epinephrine were significantly lower in cold-treated rats of the LE strain compared with cold-treated rats of the SD strain, but dipsogenic responsiveness to angiotensin II was unchanged. Although increases in the weight of the previously mentioned organs were also observed in cold-treated rats of the LE strain compared with their warm-adapted controls, weights of the heart and interscapular brown adipose tissue of both groups were significantly less than those of counterparts of the SD strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Angiotensin-related intakes of water and NaCl in Fischer 344 and Sprague-Dawley rats.

Rats of the Fischer 344 (F344) strain drank less water after either peripheral or central acute administration of angiotensin III (ANG III) than rats of the Sprague-Dawley (SD) strain. In contrast, water intakes following acute administration of ANG II were comparable in the two strains. Chronic peripheral administration of ANG II produced a salt appetite in SD but not in F344 rats; ANG III was ineffective in both strains. These data suggest that some aspects of responsiveness to ANG peptides are reduced in F344 rats. In two of three studies, water intake after acute peripheral administration of either ANG I or the beta-adrenergic agonist isoproterenol did not differ between strains; in one study, the response to both dipsogens was lower in F344 rats. Plasma renin activity was elevated to the same level by isoproterenol in both strains of rats. These results suggest that the ability of isoproterenol to release renin, the subsequent generation of ANG I, and the conversion to ANG II are similar in the two strains. However, this similarity did not extend to cardiovascular responses. Rats of the F344 strain showed a smaller decrease in blood pressure following administration of isoproterenol than did those of the SD strain. Whether this is related to differences in either the regulation of beta-adrenoreceptors or postreceptor effects in vascular smooth muscle between strains will require additional investigation.

Analysis of Variance↗
PubMed1992

Repletion of acute sodium deficit in rats drinking either low or high concentrations of sodium chloride solution.

These studies investigate the relationship between expression of sodium appetite and restoration of physiological normalcy after acute sodium depletion in Sprague-Dawley rats. After depletion (treatment with diuretic and 24 h without NaCl), separate groups of rats were allowed to drink either a low (0.03 M) or a high (0.3 M) concentration of NaCl. Intake and urinary output of sodium and selected plasma measures were made at various times up to 48 h. Depleted rats with access to 0.3 M NaCl consumed more Na+ than their deficit in the first hour and were volume expanded as a result of this excessive intake, but they continued to consume NaCl for 6-12 h. Depleted rats given 0.03 M NaCl drank a comparable volume to the 0.3 M group in the first hour and thus only approximately 10% of the solute. The intake of 0.03 M NaCl slowed after 6-12 h, at which time the cumulative intake matched the deficit and the plasma parameters had returned to nondepleted levels. Under these conditions of slow intake, it appears that sodium appetite is more closely matched to need than is the case when highly concentrated sources of sodium are available. Satiation of sodium appetite seems to require the passage of time as well as repletion of body sodium.

Animals↗
PubMed1992

Role of gonadal hormones in hypertension in the Dahl salt-sensitive rat.

The present studies examine the effect of gonadal hormones on the development of hypertension in Dahl salt-sensitive rats fed a high salt diet. In the first study, administration of estradiol benzoate did not prevent hypertension in either adult ovariectomized females or intact males. In a second study, neonatal castration of males slowed the onset of salt-induced hypertension, and females that were treated neonatally with testosterone developed somewhat higher pressures that did untreated females. These data extend to Dahl S rats the findings observed originally in spontaneously hypertensive rats that blood pressure is modulated by gonadal hormones. These results are consistent with the conclusion that gonadal hormones may exert organizational effects on cardiovascular control regions of the brain during early postnatal development in rats.

Animals↗
PubMed1992

Effect of DuP 753, a nonpeptide angiotensin II receptor antagonist, on the drinking responses to acutely administered dipsogenic agents in rats.

The present studies examine the effect of the nonpeptide angiotensin II (AII) type 1 receptor antagonist, DuP 753, on water intake in rats treated with dipsogenic stimuli, which are thought to induce drinking via release of renin and subsequent formation of AII. Subcutaneous administration of DuP 753 in doses that are known to inhibit drinking induced by AII failed to inhibit the water intake of rats following subcutaneous administration of the beta-adrenoceptor agonist isoproterenol. The peptide antagonist1 Sar, 8Ileu-AII, which blocks both AII type 1 and AII type 2 receptors, also failed to inhibit isoproterenol-induced drinking, suggesting that neither subtype is involved in this drinking response. Additional studies verified previous reports that acute subcutaneous administration of both the beta-adrenoceptor antagonist propranolol and the angiotensin I-converting enzyme inhibitor captopril could block the drinking response to subcutaneous administration of isoproterenol. Subcutaneous administration of DuP 753 also failed to inhibit the drinking responses to subcutaneous administration of serotonin, 5-hydroxytryptophan, hypertonic saline, and polyethylene glycol. However, central intraventricular administration of DuP 753 inhibited the drinking response to subcutaneous administration of isoproterenol. The results are discussed in terms of the importance of AII in mediating isoproterenol-, serotonin-, and 5-hydroxytryptophan-induced water intake and suggest a need to readdress this mechanism.

5-Hydroxytryptophan↗
PubMed1992

Effect of a reduction in sodium intake on cold-induced elevation of blood pressure in the rat.

Chronic exposure of rats to cold (5 degrees C) induces hypertension within 3 weeks. The objective of this study was to determine the effect of treatment with graded levels of dietary NaCl on the induction of hypertension during chronic exposure to cold. Four groups of male rats were used. The first, given a commercial sodium-deficient diet containing 0.30% NaCl, served as the warm-adapted control group. The second, third, and fourth groups were given the same diet containing 0.075%, 0.15%, and 0.30% NaCl, respectively. Because cold-exposed rats ingest approximately twice as much food as warm-adapted controls, this represented half, the same, and twice the amount of NaCl ingested by the control group. The latter three groups were placed in cold air (5 degrees C). All cold-treated groups had an elevation of systolic blood pressure that was proportional to the concentration of NaCl in the diet by the seventeenth week of exposure to cold. Cardiac hypertrophy occurred to the same extent in all cold-exposed groups and was thus unaffected by the NaCl content of the diet or by the extent of elevation of blood pressure. Hence, cardiac hypertrophy during chronic exposure to cold is supported by other factors, possibly by the increased concentration of either norepinephrine or triiodothyronine, or both, which occurs characteristically in rats under these conditions. The results of this experiment suggest that the amount of NaCl ingested daily plays a role in the cold-induced elevation of blood pressure observed in rats.

Acclimatization↗
PubMed1991

Potentiation of angiotensin II-induced drinking by glucocorticoids is a specific glucocorticoid type II receptor (GR)-mediated event.

Earlier studies showed that pretreatment (3 and 6 h) of rats with the glucocorticoid hormone, dexamethasone, potentiated the drinking response to either central or peripheral administration of angiotensin II (AII). In the present study the specificity and mechanisms of this potentiation were examined. Intraperitoneal (i.p.) injection of rats with the pure glucocorticoid agonist, RU 28362 (0.4-1.6 mg/kg; 3-24 h), resulted in a time- and dose-dependent potentiation of the drinking responses to either peripherally (100 micrograms/kg, s.c.) or centrally (10 ng) injected AII, similar to the effects of dexamethasone. Drinking induced by central injection of carbachol (200 ng) was unaltered by pretreatment with RU 28362, suggesting that potentiation by this compound was specific for AII. The potentiation of AII-induced drinking by either dexamethasone or RU 28362 was completely abolished by pretreatment with the glucocorticoid Type II receptor (GR) antagonist, RU 38486 (2 mg/kg, i.p.), but not by the mineralocorticoid Type I receptor (MR) blocker, mespirenone (2 mg/kg, i.p.). Taken together, these results indicate that the glucocorticoid-induced potentiation of AII-induced drinking is mediated via GR. Associated with the fact that glucocorticoids potentiate AII-induced drinking is the observation that these steroids also potentiate AII-induced urine output. This enhancement of urine output may explain in part the potentiation in drinking behavior. Possible mechanisms are discussed.

Androstanols↗
PubMed1991

Dietary intervention and training in swimmers.

To ascertain if muscle damage occurred in swimmers as a result of high-intensity training and to find if fluid and dietary manipulation could affect muscle damage, we studied 40 members of the University of Florida swimming team using creatine kinase (CK) and lactic dehydrogenase (LDH) as markers of muscle damage during a 6-month period of intensive training. During this time, training intensity, fluid intake during exercise and dietary supplementation were all modified one by one to examine their individual effects. During a control period of 4 weeks, all swimmers drank water before and during (120 min) workouts. CK in men at the end of this period averaged 315, SD 122 (normal less than 170 IU.l-1). Half of the swimmers were then given 500 ml of a glucose-electrolyte solution (GES) (Na 21 mmol.l-1, Cl 13 mmol.l-1, K 2.5 mmol.l-1, PO4 5 mmol.l-1 and glucose 6%) before workouts and twice at intervals during the workout, while half continued to drink the same volume of water. One week after division into fluid groups, the workout intensity was increased by about 10%. Another week later CK had increased to 500, SD 180 IU.l-1 in swimmers drinking water, but fell to 280, SD 105 IU.l-1 in those drinking GES (P less than 0.05). The second phase of the study began after a 4-week control period during which all athletes drank water before and during workouts. The swimmers were divided into four matched groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Changes in blood pressure and dipsogenic responsiveness to angiotensin II during chronic exposure of rats to cold.

Hypertension accompanies chronic exposure of rats to cold (5-6 degrees C). Systolic, diastolic, and mean blood pressures become elevated, and hypertrophy of the heart occurs. A previous study from this laboratory suggested that the renin-angiotensin system may play a role. The present study was carried out to assess this further. Thus, in addition to measurement of systolic blood pressure at intervals during exposure to cold, plasma renin activity and the dipsogenic responsiveness to acute administration of angiotensin II were also measured to assess the functional status of the renin-angiotensin system. The results showed a significant (p less than 0.05) increase in systolic blood pressure during the third week of exposure to cold. In contrast, plasma renin activity (PRA) increased within the first week of exposure to cold, and declined thereafter to reach the level of the control by the third week of exposure to cold. By the fourth week, PRA decreased to a level significantly (p less than 0.05) below that of the control group. The responsiveness to acute administration of angiotensin II (AII), as assessed by the drinking response, increased significantly (p less than 0.05) by the third week of exposure to cold and remained significantly elevated during the fourth week. There was a significant (p less than 0.01) direct relationship between dipsogenic responsiveness to AII and blood pressure in the cold-treated (r = .57), but not the control group (r = .12). There was also a significant (r = -.91) indirect linear relationship between PRA and dipsogenic responsiveness to AII. Cold-treated rats had significant increases in urinary norepinephrine output and weights of heart, kidneys, adrenals, and brown adipose tissue characteristic of rats acclimated to cold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1991

Bradykinin-induced dipsogenesis in captopril-treated rats.

The dipsogenic responsiveness to acute administration of the peptide, bradykinin, was studied in 4 groups of male Sprague-Dawley rats. All groups received captopril (35 mg/kg, IP) 15 minutes prior to the study. The first group then received saline (1 ml/kg, IP) while the remaining three groups received bradykinin at 50, 100 and 200 micrograms/kg, SC, respectively. The rats were placed alone into metabolic cages without food and given a preweighed bottle of tap water. Water intakes and urine outputs were then measured at 0.5, 1.0 and 2.0 hours thereafter. Bradykinin induced a dose-related increase in water intake but had no significant effect on urine output. To assess whether bradykinin might induce drinking by way of angiotensin II (AII) receptors, the AII receptor antagonist. Sar1, Ile8-AII (Sar, 300 and 600 micrograms/kg, SC) was administered to both bradykinin- (200 micrograms/kg, SC) and bradykinin plus captopril-treated (35 mg/kg, IP) groups of rats in a two-way ANOVA statistical design. Bradykinin again stimulated drinking in captopril-treated rats, but the drinking was not blocked significantly by administration of Sar. The results of this study indicate that blockade of the angiotensin I converting enzyme increases the half-life of bradykinin and unmasks its dipsogenic properties. The results suggest further that bradykinin does not appear to induce drinking via interaction with receptors for AII.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1991

Effect of a nonpeptide angiotensin II receptor antagonist, DuP 753, on angiotensin-related water intake in rats.

The effect of peripheral administration of the nonpeptide angiotensin II-1 (AII) receptor blocker, DuP 753, on the dipsogenic responses to peripherally administered angiotensins I, II, and III was tested. In all cases, DuP 753 significantly inhibited the drinking response, whether administered 15 or 45 minutes prior to administration of the dipsogen. These results suggest that the drinking responses to angiotensins I, II, and III are mediated by AII-1 receptors. They also suggest that either AIII acts via the AII-1 receptor or that DuP 753 competes at an AIII-sensitive receptor. These studies also showed that when both AII and DuP 753 were given cerebroventricularly (ICV), potent inhibition of the drinking response occurred. Further, when DuP 753 was administered peripherally and AII ICV, drinking was also inhibited. Hence, DuP 753 must penetrate the brain, at least at the circumventricular sites implicated in angiotensin-related drinking. However, centrally administered DuP 753 failed to inhibit the drinking response to peripherally administered AII. This observation is presently unexplained, but may be related to the possibility that centrally administered DuP 753 is inactivated more quickly than when it is administered peripherally. Additional studies will be required to assess this.

Angiotensin I↗
PubMed1991

Role of the sympathetic nervous system in cold-induced hypertension in rats.

Hypertension develops in rats exposed chronically to cold [6 +/- 2 degrees C (SE)] and includes both an elevation of mean arterial pressure and cardiac hypertrophy. Previous studies suggest that cold-exposed animals, at least initially, have a large sustained increase in the activity of their sympathetic nervous system, suggesting a failure of the baroreceptor system to provide sufficient negative feedback to the central nervous system. The present study was designed to investigate whether alterations in the activity of the sympathetic nervous system, including the baroreceptor reflex, occur during exposure to cold and whether they contribute to cold-induced hypertension. Twenty male rats were prepared with indwelling catheters in the femoral artery and vein. Ten of the rats were exposed to cold (6 +/- 2 degrees C) chronically, while the remaining 10 were kept at 26 +/- 2 degrees C. Withdrawal of arterial blood samples (less than 5 ml/kg), measurement of direct arterial pressures, and measurement of baroreflex function were carried out at 0800 h at intervals throughout the experiment. Norepinephrine and epinephrine concentrations in plasma were also determined at intervals throughout the experiment. Systolic, diastolic, and mean blood pressures of cold-exposed rats were increased to levels significantly above those of controls. The sensitivity of the baroreflex (delta heart period/delta mean arterial pressure) was decreased in the cold-treated group. The concentration of norepinephrine in plasma increased after 24 h of exposure to cold and remained elevated throughout the experiment, whereas the concentration of epinephrine in plasma increased initially but returned to control levels after 19 days of exposure to cold.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗