Biomedical subjects

M J Fregly

Publications and source records attributed to M J Fregly.

At least 109 records · Page 6Linked to original sources

PubMed1986

Do peripheral and cerebroventricular injections of angiotensin II act at the same site? Studies on additivity of drinking.

The urge of rats to drink following SC injections of angiotensin II (AII) far outlasts the relatively short half life of this hormone in the circulation. When water was withheld for 1 hr following SC administration of AII, water intake was similar to that of rats administered AII and given immediate access to water. Saralasin, the AII receptor antagonist, blocked this delayed drinking response, suggesting that AII receptor occupancy is critical to the appearance of the delayed drink. In contrast, the urge to drink following cerebroventricular (IVT) injection decayed within 30 min. Intravenous (IV) infusion of AII for 1 hr caused drinking during the infusion but, when water was withheld until the infusion had ended, the urge to drink decayed within 15-30 min. Additional studies tested the additivity of the drinking response to two separate doses of AII when administered peripherally and IVT. The combined administration of AII SC and IVT failed to produce clear signs of additivity over a large range of interstimulus intervals. In contrast, the combined administration of IV and IVT AII were clearly additive with respect to drinking.

Angiotensin I↗

PubMed1986

Effect of intragastric and intraperitoneal water and saline loads on the pharmacologic induction of drinking in rats.

Water intake, induced by subcutaneous (SC) administration of angiotensin II (AII, 200 micrograms/kg), isoproterenol (25 micrograms/kg), 5-hydroxytryptophan (25 mg/kg), and bethanechol (8 mg/kg), was reduced completely to control level by administration of either an intragastric (IG) or intraperitoneal (IP) load of distilled water (3% of body weight) prior to administration of the dipsogen. A similar load of isotonic saline given by both the IG and IP routes was either ineffective or only partially effective in reducing the dipsogenic response. The similar effectiveness of IP and IG loads of water in inhibiting the responsiveness to administration of dipsogenic agents argues against a gastrointestinal mechanism as an integral part of the feedback process limiting water intake in the rat. In addition, the lack of a significant effect of similar IP and IG loads of saline suggests that stretch of either the gastrointestinal or intraperitoneal spaces is not an important factor in the inhibition observed. A possibility exists that osmotic dilution, as a result of the water load, may play a role in the feedback inhibition of the drinking responses to the dipsogenic agents used in these studies, even though the responses were mediated via the AII receptor pathway rather than the osmoreceptor pathway.

5-Hydroxytryptophan↗

PubMed1986

Effect of intraperitoneal and intragastric loading with water and isosmotic solutions of saline and glucose on water intake of dehydrated rats.

Female rats, dehydrated with food available for 24 hr, lost 6 to 8% of body weight. When allowed access to water, 40 to 60% of the weight deficit was replaced within the first hr. Either intraperitoneal (IP) or intragastric (IG) water loads (3% of body weight) administered just prior to return of water inhibited water intake of dehydrated rats nearly completely during the first hr of access to water. In contrast, similar loads of isotonic saline were much less effective. Even when 0.5 and 1.0 hr elapsed between IP loading (3% of body weight) with isotonic saline and access to water, water intake was not significantly different from that of untreated, dehydrated controls. In contrast, a similar IP load of water at these times completely inhibited water intake. Because of the contrasting effects of similar loads of water and isotonic saline on water intake of dehydrated rats, additional studies were carried out with an isosmotic solution of glucose (5%). IG administration (3% of body weight) of glucose inhibited water intake of dehydrated rats. IP administration (3% of body weight) attenuated the drinking response but did not reduce it to the level observed in dehydrated rats given an IP water load. When isosmotic glucose was administered at 0.5, 1.0, and 2.0 hr prior to allowing access to water, water intake was reduced significantly below that of dehydrated controls and to the same extent regardless of time of administration of the glucose load.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Catecholamine excretion and beta-adrenergic responsiveness in estrogen-treated rats.

Chronic treatment with an estrogenic agent is known to reduce the responsiveness to beta-adrenergic stimulation in rats. To assess the possibility that endogenously produced catecholamines may play a role in this phenomenon, female rats were treated either with implanted Silastic tubes containing estradiol benzoate (26 micrograms/kg/day) or with empty tubes. After 12 weeks of treatment, the dipsogenic, colonic temperature and tail skin temperature responses to acute administration of the beta-adrenoceptor agonist, isoproterenol, were blunted compared to controls. Each of these responses was negatively correlated with serum estradiol concentration measured by radioimmunoassay. Urinary norepinephrine output was elevated significantly in treated rats during a 24-hour basal period. During a 2-hour exposure to air at 4 degrees C, urinary outputs of norepinephrine, epinephrine, and dopamine were elevated significantly above those of controls. There were significant positive correlations between plasma estradiol concentration and the outputs of each of the above catecholamines during the 24-hour basal period and during cold exposure, with norepinephrine being the most strongly correlated. Dipsogenic and metabolic (tail skin and colonic temperature) responses to administration of isoproterenol were negatively correlated with catecholamine excretion during both the basal 24-hour period and during cold exposure. These results suggest that reduced beta-adrenergic responsiveness in estrogen-treated rats may have resulted from down-regulation of beta-adrenoceptors associated with increased secretion of catecholamines induced by chronic estrogen treatment.

Animals↗

PubMed1986

Beta-adrenergic responsiveness in the rat following acute administration of ethanol.

Ethanol has been shown to induce a hypothermia in rats maintained in air at 26 degrees C. The objective of the present study was to assess the metabolic responsiveness of ethanol-treated rats to administration of isoproterenol, a beta-adrenoceptor agonist, and to assess whether ethanol per se, or the hypothermia accompanying its administration, contribute to changes in beta-adrenergic responsiveness. In the present study, administration of ethanol (3 g/kg, i.p.) reduced both colonic temperature (Tco) and rate of oxygen consumption (metabolic rate) of rats maintained at 26 degrees C to levels below those of saline-treated controls within 20 min after treatment. Maximal decreases in both parameters occurred within approximately 40 min. Administration of isoproterenol (50 micrograms/kg, s.c.) 10 min after treatment with either ethanol or saline was accompanied by an increase in the metabolic rates of both groups, although the magnitude of the increase in the ethanol-treated group was less than that of controls. Maximal increases in tail skin temperatures (Tsk) following treatment with isoproterenol were similar in both groups but an increase in Tsk occurred earlier in the ethanol-treated group. Tco increased after treatment with isoproterenol in the saline-treated group but decreased in the ethanol-treated group. When isoproterenol was administered 90 min after treatment with ethanol, increases in metabolic rate, Tsk, and Tco were similar in both groups, although the increase in Tsk of ethanol-treated animals was delayed until Tco reached pretreatment level. Exposure to 30 degrees C minimized ethanol-induced hypothermia. At this temperature the metabolic responses to administration of isoproterenol at 90 min after treatment with ethanol did not differ significantly between the two groups. These results suggest that the metabolic responsiveness to administration of a beta-adrenoceptor agonist is not altered by prior treatment with ethanol but is affected by the hypothermia accompanying its administration.

Animals↗

PubMed1986

Effect of chronic treatment with estrogen and thyroxine, alone and combined, on the rate of deiodination of L-thyroxine to 3,5,3'-triiodothyronine in vitro.

The effect of administration of thyroxine (T4) and estradiol benzoate (EB), alone and combined (EB + T4), to female rats for 35 days on their serum concentrations of T4 and triiodothyronine (T3), and on the rate of conversion of T4 to T3 by homogenates of their liver and kidneys was studied. Administration of T4 (50 micrograms/kg b.w./day) resulted in an increase, while administration of EB (57 micrograms/kg b.w./day) resulted in a decrease in serum levels of T4. In EB + T4-treated rats, the serum concentration of T4 was less than that of either the T4-treated or control groups, while the serum T3 concentration was greater than that of the EB-treated group. Administration of T4 resulted in a rate of hepatic generation of T3 which was 180% of control, while the rate of renal T3 generation was 152% of control. Activity of T4 5'-monodeiodinase in hepatic homogenates was not affected significantly by administration of EB, while that in renal homogenates was inhibited by 44%. Administration of T4 in combination with EB resulted in a rate of conversion of T4 to T3 by hepatic homogenates which was 334% of control and significantly higher than that achieved by T4 alone. The rate of renal T3 generation by this group was 129% of control, but less than that achieved by administration of T4 alone. Administration of EB + T4 potentiated the effect of T4 on hepatic T4 to T3 converting activity and is likely responsible for the reduction in serum T4 concentration of these animals.

Animals↗

PubMed1986

Physiologic responses to chronic dietary tyrosine supplementation in DOCA-salt-treated rats.

The antihypertensive effect of chronic administration of L-tyrosine (Tyr) was investigated in a two-part study. In the first experiment, adult male Sprague-Dawley rats were assigned to 1 of 4 treatment groups: control diet plus unilateral nephrectomy (Nphx) and 0.15 M NaCl (Sal) as the sole drinking solution (C-CTRL); control diet plus deoxycorticosterone acetate (DOCA, 268 micrograms/rat/day), Nphx, and Sal (C-DOCA); control diet supplemented with 2.5% L-p-Tyr plus Nphx and Sal (Tyr-CTRL), and Tyr plus DOCA, Nphx, and Sal (Tyr-DOCA). Systolic blood pressure (SBP) increased within 2 weeks after initiation of treatment with DOCA-salt and remained elevated throughout the duration (8 weeks) of the study (p less than 0.001). Dietary administration of Tyr to DOCA-treated rats failed either to affect SBP in normotensive rats or the elevation of SBP in DOCA-treated rats. Dietary supplementation with Tyr induced a significant elevation in urinary excretion of free dopamine (week 1, 3, 5, and 7) and a decreased excretion of free norepinephrine (week 1) without regard to DOCA treatment. Metabolic responsiveness (change in colonic temperature) and cardiovascular responsiveness (change in heart rate) to subcutaneous administration of the beta-adrenergic agonist, isoproterenol, were significantly prolonged while alpha 2-adrenoceptor number (cerebral cortical membranes; 3H-yohimbine binding) was reduced in rats receiving Tyr. In the second experiment, similar rats were assigned to 1 of 3 treatment groups: control diet plus Nphx and Sal, control diet plus Nphx, DOCA and Sal, and Tyr plus DOCA, Nphx, and Sal; however, Tyr was not started until DOCA-salt-induced hypertension developed (4 weeks). Neither acute (2.5 h post-meal) nor chronic (4 weeks) effects of administration of Tyr on SBP were noted. Thus, the Tyr-induced changes observed in these studies include a chronic increase in free dopamine, and a transient decrease in norepinephrine, excretion. No significant effects of Tyr on blood pressure of DOCA-salt-treated rats were observed.

Animals↗

PubMed1986

Effect of chronic treatment with deoxycorticosterone acetate on content of a natriuretic substance in atria of rats.

Chronic (72 days) administration of deoxycorticosterone acetate (DOCA), with or without saline as the sole drinking fluid, depleted atria of rats of their diuretic and natriuretic activities. Chronic ingestion of saline as the sole drinking fluid did not affect the diuretic, natriuretic, and kaliuretic activities of atria compared with those of rats receiving water to drink. Since systolic blood pressure of the DOCA-treated group did not differ significantly from that of the untreated control group, the decrease in potency of atrial extract from DOCA-treated rats most likely occurred in response to increases in extracellular and vascular volumes. The ability of DOCA to decrease diuretic and natriuretic activities of atria was dose dependent. The decreased activities of the atria of DOCA-treated rats could reflect an increased production and turnover of atrial natriuretic factor. Additional studies revealed an increased diuretic and natriuretic responsiveness of DOCA-treated recipients to atrial extract from untreated rats. Thus, the results of these studies suggest that chronic treatment with DOCA reduced the natriuretic and diuretic potencies of atrial extract and increased renal responsiveness to it.

Animals↗

PubMed1985

Reduced dipsogenic responsiveness to intracerebroventricularly administered angiotensin II in estrogen-treated rats.

Chronic administration of two doses of estradiol benzoate (30 and 46 micrograms/kg/day) reduced the drinking response to acute administration of either isoproterenol (25 micrograms/kg, s.c.), the beta-adrenergic agonist, or angiotensin II (Ang II) (200 micrograms/kg, s.c.). The drinking response to intracerebroventricular administration of Ang II (40 ng/kg), but not carbachol (800 ng/kg), was also attenuated in estrogen-treated rats. An assessment of the Ang II binding in a diencephalic block of tissue from estrogen-treated rats revealed a significant reduction compared to untreated controls. The results suggest, but do not prove, that the reduced drinking response observed in estrogen-treated rats may be related to a reduction in the number of Ang II receptors in the brain.

Angiotensin II↗

PubMed1985

m-Octopamine: normal occurrence with p-octopamine in mammalian sympathetic nerves.

The development of a radiochemical enzyme assay for p-octopamine in 1969 led to its identification in a large number of invertebrate nerve systems and in mammalian sympathetic nerves. The original method by which p-octopamine was measured has now been found to be nonspecific; however, modifications of this procedure can determine both m- and p-octopamine. We recently developed a new specific method for the unequivocal identification and quantitative determination in tissue of the six octopamine and synephrine isomers. With this method--negative chemical ionization gas chromatography-mass spectrometry--the more physiologically active m-octopamine has been found in association with p-octopamine in 10 organs of the rat. m-Octopamine is present in concentrations equal to those of p-octopamine in heart, spleen, and liver and in concentrations from 30 to 60% of p-octopamine in adrenals, vas deferens, brain, kidney, large intestine, bladder, and lungs. In vivo inhibition of monoamine oxidase markedly increased the concentrations of both m- and p-octopamine in all organs examined. Both amines were virtually absent from all organs except the adrenals following chemical sympathectomy with 6-hydroxydopamine, thereby establishing that m- and p-octopamine are localized within sympathetic nerve endings.

2-Hydroxyphenethylamine↗

PubMed1985

Role of renin-angiotensin-aldosterone system in NaCl appetite of rats.

A variety of experimental paradigms is now known to induce an appetite for NaCl solutions in rats. These include 1) bilateral adrenalectomy; 2) hypothyroidism; 3) salivariectomy; and 4) administration of hydrochlorothiazide, metyrapone, estrogen, methylxanthines, captopril, propranolol, large doses of deoxycorticosterone acetate, and intraperitoneal isotonic glucose or subcutaneous polyethylene glycol. A point of commonality among these is that a reduction in preference threshold accompanies the appetite for NaCl in all cases thus far tested. An additional point is the fact that each paradigm inducing a salt appetite, except salivariectomy, can be linked to an effect on the renin-angiotensin-aldosterone system. The level of angiotensin II in the brain may play a role in the induction of a salt appetite in the rat. It is clear, however, that modest doses of mineralocorticoid hormones, given in conjunction with the stimulus producing the salt appetite (e.g., adrenalectomy, thyroidectomy, or treatment with captopril), reduces NaCl intake to control level. Although this effect can be partially explained in most cases by the consequent reduction in angiotensin II production, the salt appetite that occurs when mineralocorticoid concentration in blood is high and angiotensin II concentration is low, or when both are low, requires another explanation. This may be related to the effect of mineralocorticoid hormones on salivary sodium concentration. The role of the concentration of sodium in saliva on intake of NaCl solution provides an alternative explanation for the induction of a salt appetite in rats and merits additional study.

Adrenalectomy↗

PubMed1985

Nycthemeral rhythms and sodium chloride appetite in rats.

Adrenalectomized rats maintained on a 12:12 light-dark cycle drank large amounts of 0.3 M NaCl solution during the night. They showed virtually no NaCl appetite during the day. As a result of their high day natriuresis, the adrenalectomized rats sustained a negative Na+ balance during the day about three times that of controls. This was offset by a correspondingly higher positive Na+ balance at night. In a second experiment in intact rats, the latency to exhibit NaCl appetite during polyethylene glycol-induced hypovolemia was shorter when the treatment was administered in the evening than in the morning. This again demonstrates a relative facilitation of NaCl intake at night and suggests a major nycthemeral interaction with putative physiological stimuli of NaCl appetite.

Adrenalectomy↗

PubMed1985

Angiotensin II-induced hypothermia in rats.

Systemic administration of angiotensin II (ANG II) (200 micrograms/kg sc) to the rat induced a hypothermic response that was characterized within 12 min by a reduction in the rate of O2 consumption, vasodilation of the tail, and a 1.3 degrees C fall in colonic temperature. Administration of ANG II in doses ranging from 10 to 200 micrograms/kg resulted in a decrease in colonic and an increase in tail skin temperature. Angiotensin I (ANG I) (200 micrograms/kg sc) induced a similar hypothermic response which was abolished by pretreatment with the ANG I-converting enzyme inhibitor, captopril (35 mg/kg ip). The interaction of ANG II with cholinergic and adrenergic pathways was evaluated to determine possible mechanisms. Treatment with ANG II (200 micrograms/kg sc) and propranolol, a beta-adrenoceptor antagonist (6 mg/kg ip), resulted in a greater depression of colonic temperature (Tco) than was observed with ANG II alone but did not affect the increase in tail skin temperature (Tsk) accompanying administration of ANG II. When ANG II was administered in combination with the beta-adrenergic agonist, isoproterenol (50 micrograms/kg ip), Tco remained at control levels, whereas an enhancement of the ANG II-induced increase in Tsk occurred. Administration of ANG II in combination with atropine sulfate (6 mg/kg ip), a muscarinic receptor antagonist which crosses the blood-brain barrier, significantly reduced the extent of the fall in Tco without affecting the increase in Tsk. The combined treatment of ANG II and the quaternary analogue, atropine methyl nitrate (3.25 mg/kg ip), which does not cross the blood-brain barrier, failed to affect the hypothermic responses to ANG II. These results suggest that the hypothermic responses to ANG II may be mediated through a central cholinergic pathway and possibly influenced by an adrenergic component. The inability of both adrenergic and cholinergic blockers to affect the vasodilatory response of the tail of the rat to administration of ANG II suggests that the mechanisms subserving heat production can be blocked independently of those subserving heat loss.

Angiotensin II↗

PubMed1985

Effect of l-p-tyrosine on the development of renal hypertension in rats.

Dietary administration of tyrosine (0.25-2.50%) to rats whose kidneys were bilaterally encapsulated with latex envelopes provided modest protection against the development of hypertension. Elevation of blood pressure was slower (one experiment) and maximal level attained was reduced (two experiments) compared to untreated, renal encapsulated controls. In addition, the polydipsia, polyuria, and reduced renal concentrating ability characteristically accompanying hypertension were attenuated. The mechanism(s) accounting for the partial protection against hypertension reported here is unknown although administration of tyrosine was accompanied by a reduced cardiovascular responsiveness to graded doses of phenylephrine.

Animals↗

PubMed1985

Effect of chronic administration of deoxycorticosterone acetate on salt appetite of captopril-treated rats.

Chronic dietary administration of the angiotensin I-converting enzyme inhibitor, captopril (1.0 g/kg food), induced an appetite for 0.15 M NaCl solution relative to distilled water in a two-bottle ad libitum access paradigm. Graded doses of deoxycorticosterone acetate (DOCA) were administered to the captopril-treated rats via Silastic tubes implanted sc. A U-shaped dose-response relationship was observed between dose of DOCA and intake of 0.15 M NaCl solution. The lowest intake of NaCl occurred with a dose of 102.1 micrograms DOCA/day (333 micrograms/kg X day). Water and food intakes were not affected significantly. At the end of the first week of treatment with DOCA, pilocarpine (3.0 mg/kg, ip.)-stimulated salivary chloride concentration was measured. The relationship between salivary chloride concentration and mean intake of 0.15 M NaCl solution was also U shaped, with the minimal NaCl intake associated with a salivary chloride concentration of 54 meq/liter. During the second week of treatment with DOCA, all rats were offered a choice between 0.25 M NaCl solution and distilled water. Rats receiving DOCA at doses of 102.1 micrograms/day or greater had a significantly lower intake of NaCl solution than those receiving either captopril alone or 66.5 micrograms DOCA/day in combination with captopril. These results indicate that the appetite for NaCl solution induced by captopril can be inhibited by concurrent administration of DOCA. They also suggest that changes in the concentration of electrolytes in saliva may be associated with changes in the appetite for NaCl solution.

Animals↗

PubMed1985

Disruption of estrous cycles in exercise-trained rats.

The female Sprague-Dawley rat was evaluated as an animal model for the menstrual irregularities that are common in women athletes. Daily vaginal smears revealed that estrous cycles were markedly disrupted in rats during a 10-week exercise training program, while cycles remained normal in sedentary rats. Compared to 9 sedentary rats, the 10 exercise-trained rats had longer mean cycle lengths and fewer estrus smears. Six of the exercise-trained rats, but none of the sedentary rats, had an "anestrus period" with more than twice the normal interval between estrus smears; one exercise-trained rat became essentially acyclic. Weight gain during the 10-week training program was lower in exercise-trained rats than in sedentary rats. Colonic temperatures, monitored at rest and during 30 min of exercise, were slightly lower in exercise-trained rats with irregular estrous cycles than in exercise-trained rats with regular cycles, indicating that unusually elevated body temperatures during exercise are not responsible for exercise-related reproductive acyclicity. It is concluded that the female Sprague-Dawley rat may be a useful animal model for the study of menstrual irregularities associated with exercise training.

Anestrus↗

PubMed1985

Inhibition of sodium transport in frog skin and iodination of tyrosine in vitro by a peptide of renal origin.

Eluates from a Sephadex G-25 column through which dog renal homogenate was passed contained a factor that inhibited lactoperoxidase (LPO)-catalyzed iodination of tyrosine as well as the short circuit current (active absorptive sodium flux) in isolated skin of the bullfrog (Rana catesbeiana). The active fraction also had a sulfhydryl-containing moiety, the concentration of which was correlated directly with the extent of inhibition of the LPO enzyme. The fractions active in inhibition of the LPO enzyme failed to affect the Na/K-AT-Pase enzyme. Whether the same moiety of the active fraction inhibits both the LPO enzyme and SCC in frog skin is unknown and awaits additional study.

Animals↗

PubMed1984

Clonidine antagonism of angiotensin-related drinking: a central site of action.

Administration of either isoproterenol (25 micrograms/kg, s.c.) or angiotensin II (200 micrograms/kg, s.c.) induces drinking in rats within 0.5-1 h. This drinking was inhibited by prior administration of the presynaptic alpha-adrenergic agonist clonidine (12 micrograms/kg, i.p.). Urine output was enhanced by clonidine in the angiotensin II-, but not the isoproterenol-treated group. Drinking in response to peripheral administration of either angiotensin II or isoproterenol was also inhibited by intracerebroventricular (i.v.t.) administration of clonidine (8 micrograms/kg). This dose of clonidine also enhanced the urine output after angiotensin II. Further, the drinking induced by i.v.t. administration of angiotensin II, at 4 but not 20 ng/kg was inhibited by peripheral administration of clonidine (12 micrograms/kg, i.p.). When clonidine was administered i.v.t. prior to i.v.t. injection of either angiotensin II (20 ng/kg) or carbachol (1.2 micrograms/kg), the drinking response to these dipsogens was attenuated. These results suggest that clonidine may act centrally to attenuate drinking at a site, possibly in the nucleus tractus solitarius, that may be considered a final common pathway for this response.

Angiotensin II↗