PubMed Health⌕ Search

Biomedical subjects

M J Fregly

Publications and source records attributed to M J Fregly.

At least 127 records · Page 7Linked to original sources
PubMed1984

A role for presynaptic alpha 2-adrenoceptors in angiotensin II-induced drinking in rats.

Studies from this laboratory have shown that either central or peripheral administration of clonidine, the alpha 2-adrenoceptor agonist, can attenuate a variety of dipsogenic stimuli in rats. Further, yohimbine and tolazoline, alpha 2-adrenoceptor antagonists, augment the drinking response to both peripherally administered isoproterenol and angiotensin II. Studies reported here establish a dose-inhibition relationship between the dose of clonidine administered (2 to 32 micrograms/kg) intracerebroventricularly (IVT) and inhibition of the drinking response to peripherally administered angiotensin II (200 micrograms/kg. SC). DI50 was approximately 4 micrograms/kg. Yohimbine (300 micrograms/kg, SC) reversed the antidipsogenic effect of centrally administered clonidine (32 micrograms/kg, IVT) on angiotensin II-induced (200 micrograms/kg, SC) water intake. Phenylephrine, an alpha 2-adrenoceptor agonist, administered IVT (40 and 80 micrograms/kg) also inhibited angiotensin II-induced drinking in a dose-related fashion. The antidipsogenic effect of phenylephrine (80 micrograms/kg) was blocked by administration of yohimbine (300 micrograms/kg. SC). Thus, this effect of phenylephrine most likely occurs by way of alpha 2-adrenoceptors. These results support a role for the pre-synaptic alpha 2-adrenoceptor in the mediation of drinking in rats. Activation of alpha 2-adrenoceptors is accompanied by reduced water intake while inhibition of these receptors enhances water intake.

Angiotensin II↗
PubMed1984

Effect of intracerebroventricularly administered octopamines and synephrines on angiotensin II-induced water intake in rats.

Recent studies from this laboratory showed that l-m-synephrine (phenylephrine), a metabolite of l-m-octapamine, inhibited the drinking response of rats to peripherally administered angiotensin II. The objective of this investigation was to determine whether the isomers of both octapamine and synephrine could inhibit angiotensin II-induced dipsogenesis in the rat. Of the isomers tested, only d,l-m-octopamine and l-m-synephrine blocked the dipsogenic response to administration of angiotensin II (200 micrograms/kg, SC). The antidipsogenic effect of both d,l-m-octopamine and l-m-synephrine could be blocked by concurrent administration of yohimbine (300 micrograms/kg, IP), an alpha 2-adrenoceptor antagonist. The results indicate that m-octopamine and m-synephrine exert their antidipsogenic effect via alpha 2-adrenoceptors. These studies add to a growing body of data suggesting that activation of alpha 2-adrenoceptors inhibits, while blockade of these receptors enhances, angiotensin II-induced drinking.

2-Hydroxyphenethylamine↗
PubMed1984

Effect of beta-adrenergic antagonists on the spontaneous appetite for NaCl solution in rats.

Chronic dietary administration of the beta-adrenergic antagonist, propranolol (1.6-2.0 g/kg), to both male and female rats induced an appetite for 0.25 M NaCl solution when the rats were offered a choice between distilled water and salt solution to drink. Treatment was also accompanied by a significant reduction in both water and food intakes. In addition, increases in intake of NaCl solution during treatment with propranolol were correlated significantly with increases in urinary sodium output. To test for completeness of beta-adrenergic blockade, treated and control rats in the first study were administered isoproterenol (25 micrograms/kg b.w., SC) acutely and given only water to drink. The increased 1 hr water intake characteristically accompanying acute administration of isoproterenol was blocked completely by propranolol. Additional experiments were carried out with butoxamine, a selective beta 2-adrenoceptor antagonist, (1.5 and 3.0 g/kg of food) to determine its effect on intake of 0.25 M NaCl solution. Butoxamine failed to produce a significant effect on salt appetite. The results indicate that chronic treatment with propranolol, but not butoxamine, induces an appetite for NaCl solution. They further suggest, but do not prove, that beta 1-adrenoceptors may be involved in the appetite for NaCl solutions in rats.

Adrenergic beta-Agonists↗
PubMed1984

Drinking: a final common pathway?

Administration of either naloxone, an opioid antagonist (1 mg/kg i.p.), or clonidine, an alpha 2 adrenoceptor agonist (12 micrograms/kg i.p.), attenuated the dipsogenic responses of female rats to both angiotensin II (200 micrograms/kg s.c.) and isoproterenol (25 micrograms/kg s.c.). The effect of simultaneous administration of naloxone and clonidine at these submaximal doses was an additive attenuation of both angiotensin II- and isoproterenol-induced water intakes. The absence of a significant interaction between naloxone and clonidine to inhibit drinking suggests that they act by a similar mechanism. Yohimbine, an alpha 2 adrenoceptor antagonist (300 micrograms/kg i.p.), administered in combination with naloxone, reversed the antidipsogenic effect on angiotensin II-induced drinking. These results provide further support for a role for alpha 2-adrenoceptors in laboratory-induced drinking in rats, and suggest the possibility that the antidipsogenic effect of naloxone is related to alpha 2 adrenergic mechanisms. A model to support these observations is presented in which two separate pathways for the induction of drinking (osmoreceptor- and angiotensin II-induced) converge on a final common pathway. Since both naloxone and clonidine inhibit responses to stimulation of both pathways for drinking, these results suggest that their actions are likely to be at some point as yet undetermined on the final common pathway.

Angiotensin II↗
PubMed1984

Effects of chronic estrogen treatment on water exchange in rats.

Intact female rats implanted subcutaneously with Silastic tubes containing estradiol benzoate (EB) (28.7 micrograms X kg-1 X day-1) for 28 wk had a significantly greater daily intake of water, a higher water-to-food intake ratio, and a greater urine output than untreated control rats. Ovariectomized (OVX) rats also implanted for 14 wk with EB tubes (15 and 36 micrograms X kg-1 X day-1) showed identical results. Dipsogenic responses of the EB-treated rats to isoproterenol (25 micrograms/kg sc), angiotensin II (200 micrograms/kg ip), and hypertonic saline (1 M, 1% of body wt ip) were significantly attenuated. Both intact and OVX rats were subjected to a 24-h dehydration to assess renal concentrating ability. EB-treated rats lost significantly more weight and excreted significantly more urine of lower osmolality than controls. Administration of vasopressin to volume-loaded, EB-treated rats revealed no abnormalities in the ability to concentrate urine to the level of controls. Thus, in spite of a reduced responsiveness to several dipsogenic stimuli, EB-treated rats have an increased daily water turnover apparently related to an inability to concentrate their urine. This in turn may be related to abnormalities in either synthesis or release of antidiuretic hormone or both.

Angiotensin II↗
PubMed1984

Effect of an exercise regimen on development of hypertension in rats.

The possibility that a forced exercise regimen might prevent the development of hypertension induced in rats both by renal encapsulation and chronic administration of deoxycorticosterone acetate (DOCA) and NaCl has been studied. In renal hypertensive rats, forced exercise at 0.4 to 1.25 miles/day, 7 days/wk for 16-22 wk failed to prevent the development of hypertension and cardiomegaly and reduced renal concentrating ability accompanying the hypertension. In DOCA-treated rats (10 mg/wk), forced exercise at 0.4 and 0.8 mile/day, 7 days/wk for 16 wk also failed to prevent both the development of hypertension and cardiomegaly. A review of data of others reveals that exercise may delay the development of hypertension in both Dahl salt-sensitive and spontaneously hypertensive (SHR) rats and may modestly reduce the maximal level of pressure attained. Of the four models of hypertension studied to date in rats, the Dahl salt-sensitive strain appears to be the one that responded best to exercise, although blood pressure eventually reached that of sedentary controls.

Animals↗
PubMed1984

Response to thermal stress in the rat following acute administration of ethanol.

Several thermoregulatory responses (i.e., colonic temperature, tail-skin temperature, rate of oxygen consumption) were measured in the rat following acute administration of either saline or 3 g ethanol/kg BW i.p. at ambient temperatures (Ta) of 17, 25, and 32 degrees C. The magnitude of the ethanol-induced, hypothermic response was inversely related to Ta, with the decrease in colonic temperature (Tco) at 120 min postinjection ranging from 0.1 degree C at Ta 32 degrees C to 3.2 degrees C at Ta 17 degrees C. Depression of rate of oxygen consumption (heat production) was a major factor contributing to ethanol-induced hypothermia, with no observed differences in heat loss as assessed by differences in the responses of tail skin temperature. Thermoregulatory responses were also measured following acute administration of ethanol at Ta 25 degrees C and immediate exposure to either Ta 32 or 17 degrees C. The increase in Tco of ethanol-treated rats was delayed compared to controls following exposure to 32 degrees C. In addition, tail skin temperature and rate of oxygen consumption of treated rats were significantly lower. The delayed rise in Tco is most likely the result of a reduction in rate of oxygen consumption. When administered ethanol at Ta 25 degrees C and then exposed to Ta 17 degrees C, the rats exhibited a significant recovery from the metabolic depression that characterized the administration of ethanol during exposure to Ta 17 degrees C. This was most likely related to differences in the clearance of ethanol from blood. The results of this study are consistent with the suggestion that the physiologically significant inhibitory effect of acute administration of 3 g ethanol/kg BW on thermoregulatory responses of rats is manifested at the level of heat production rather than heat loss and that the effect is exacerbated by a reduction in Ta.

Animals↗
PubMed1983

On the mechanism of serotonin-induced dipsogenesis in the rat.

Subcutaneous administration of l-5-hydroxytryptophan (5-HTP), the precursor of serotonin, to female rats induces copious drinking accompanied by activation of the renin-angiotensin system. Neither a reduction in blood pressure nor body temperature accompanied administration of 5-HTP. The objective of the present study was to determine whether serotonin-induced dipsogenesis, like that of 5-HTP, is mediated via the renin-angiotensin system. Serotonin (2 mg/kg, SC)-induced drinking was inhibited by the dopaminergic antagonist, haloperidol (150 micrograms/kg, IP), which also inhibits angiotensin II-induced drinking. Both captopril (35 mg/kg, IP), an angiotensin converting enzyme inhibitor, and propranolol (6 mg/kg, IP), a beta-adrenergic antagonist, blocked serotonin-induced dipsogenesis. The alpha 2-adrenergic agonist, clonidine (6.25 micrograms/kg, SC), which suppresses renin release from the kidney, attenuated serotonin-induced water intake. The dipsogenic responses to submaximal concentrations of both serotonin (1 mg/kg, SC) and isoproterenol (8 micrograms/kg, SC) were additive rather than interactive suggesting that similar pathways mediate both responses. The serotonergic receptor antagonist, methysergide (3 mg/kg, IP), inhibited serotonin-induced drinking but had no effect on isoproterenol (25 micrograms/kg, SC)-induced dipsogenesis. However, neither serotonin (2 mg/kg, SC) nor isoproterenol (25 micrograms/kg, SC)-induced drinking was inhibited by cinanserin (25 micrograms/kg, IP). These data indicate that serotonin induces drinking in rats via the renin-angiotensin system. However, the results of the studies using methysergide suggest that serotonin appears to act at a point prior to activation of beta-adrenoceptors in the pathway leading to release of renin from the kidneys.

Animals↗
PubMed1983

Effects of yohimbine and tolazoline on isoproterenol and angiotensin II-induced water intake in rats.

Subcutaneous administration of the alpha 2-adrenoreceptor antagonists, yohimbine and tolazoline, at doses up to 1000 micrograms/kg, had no effect on water intake of female rats. However, when these compounds were administered SC in combination with either the beta-adrenoreceptor agonist, isoproterenol (10 to 25 micrograms/kg, SC), or with angiotensin II (200 micrograms/kg, SC), water intake was enhanced. In contrast, intraventricular administration of either tolazoline (10 and 20 micrograms/kg) or yohimbine (300 micrograms/kg) failed to augment the dipsogenic response to angiotensin II (150 micrograms/kg, SC). Thus, the enhancing effect of these alpha 2-adrenoreceptor antagonists on isoproterenol- and angiotensin II-induced water intakes appears to be manifested peripherally, rather than centrally. In view of the fact that clonidine, an alpha 2-adrenoreceptor agonist, has been shown to inhibit water intake induced by both isoproterenol and angiotensin II, the results suggest that the alpha 2-adrenoreceptor may play a role in modulating water intake induced by these two dipsogenic agents.

Angiotensin II↗
PubMed1983

Effect of acute administration of isoproterenol and angiotensin II, separately and in combination, on water intake and blood pressure of rats.

The effects of administration of isoproterenol, a beta-adrenergic agonist, and angiotensin II, a peptide, separately and in combination, on water intake and blood pressure of rats were studied. The results of 6 factorially designed studies in which 4 different doses of each compound were administered revealed that water intakes increased directly with the logarithm of increasing doses of each. The effect of simultaneous administration of the 2 compounds on water intake was additive at submaximal doses of each. No interactive effects on water intake were observed when the 2 compounds were administered simultaneously in any study. Reduction in urine output appears to be a more sensitive response to administration of isoproterenol than increase in water intake since it was virtually abolished at a dose (2.5 micrograms/kg SC) that had no effect on water intake. The lowest doses of angiotensin II (25 and 50 micrograms/kg SC) had no significant effect on either water intake or urine output. The effect of simultaneous administration of both compounds on urine output was essentially the same as that accompanying administration of isoproterenol alone. Following administration of angiotensin II (150 micrograms/kg, SC) mean systemic blood pressure of unanesthetized, chronically cannulated rats reached maximal levels within 5 min and returned to pretreatment control level by 60 min. Following administration of isoproterenol (25 micrograms/kg, SC), mean systemic blood pressure decreased within 5 min, was maximally depressed by 30 min and had returned halfway to the pretreatment control level by 60 min. Simultaneous administration of isoproterenol and angiotensin II failed to induce a significant change in blood pressure. These results are of particular interest since they show that neither the pressor effect of angiotensin II nor the depressor effect of isoproterenol is essential for the induction of drinking by these 2 compounds.

Angiotensin II↗
PubMed1983

Effect of chronic treatment with captopril on reactivity of aortic smooth muscle from normotensive and renal hypertensive rats.

Acute administration of the angiotensin I converting enzyme inhibitor, captopril (2 X 10(-4) M), was shown in an earlier study to attenuate the contractile responses of aortic rings of rats to alpha-adrenergic agonists in vitro. The objective of the present study was to determine the effect of chronic treatment with captopril on reactivity of aortic rings from both normotensive and renal hypertensive rats when captopril was no longer present. Four groups of rats were used: (1) normotensive, untreated; (2) normotensive, captopril-treated (48 mg/kg b.w. per day for five weeks); (3) hypertensive (bilateral renal encapsulation for five weeks), untreated and (4) hypertensive, captopril-treated. Renal encapsulation was associated with a significant increase in systolic blood pressure, which was prevented by concomitant treatment with captopril. At the end of the five weeks treatment aortic rings, 4 mm in length, were washed for 2 h to remove the captopril, following which contractile responses to various vasoactive agents were studied in vitro. Chronic treatment with captopril attenuated significantly contractile responses to both norepinephrine (10(-9) to 10(-5) M) and phenylephrine (10(-8) to 10(-4) M) but had no effect on isoproterenol-induced relaxation of KCl-depolarized tissue in the presence of 10(-5) M phentolamine. Contractile responses to angiotension I (10(-10) to 10(-7) M) did not differ statistically among the four groups. Following addition of captopril (2 X 10(-4) m) to the bath for 30 min, contractile responses to angiotensin I were attenuated in all four groups of rings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1983

Water deprivation-induced drinking in rats: role of angiotensin II.

The role of angiotensin II in the control of water intake following deprivation of water for varying lengths of time was studied. Male rats were deprived of water for 0, 12, 24, 36, or 48 h. Water intakes were measured with and without pretreatment with the angiotensin I-converting enzyme inhibitor, captopril (50 mg/kg, ip). Captopril had no significant effect on water intake following either 0 or 12 h of water deprivation. However, captopril significantly attenuated water intake following 24-48 h of water deprivation with the magnitude of the attenuation increasing as the length of the period of water deprivation increased. Plasma renin activity was significantly increased over control levels after 24-48 h of water deprivation but not after 12 h of water deprivation. Plasma renin activity tended to increase as the length of the water-deprivation period increased. Serum osmolality and sodium concentration were significantly increased over control levels following 12-48 h of water deprivation. Serum osmolality and sodium concentration failed to show any further increases with increasing length of water deprivation beyond the increases following 12 h of water deprivation. The data indicate that the water intake of water-deprived rats can be divided into an angiotensin II-dependent component and angiotensin II-independent component. The angiotensin II-independent component appears to be more important in the early stages of water deprivation whereas the angiotensin II-dependent component becomes more important as the length of the water-deprivation period increases.

Angiotensin II↗
PubMed1983

Changes in vascular responsiveness following chronic exposure to cold in the rat.

The responsiveness of smooth muscle from rings of aortic tissue of cold-acclimated (CA, 6 degrees C, 5-15 wk) rats to both alpha- and beta-adrenergic agonists and KCl was tested and compared with that of warm-adapted (25 degrees C) controls. alpha-Adrenergic stimulation, induced by low doses (10(-8)-10(-7) M) of phenylephrine and norepinephrine in the presence and absence of the beta-adrenergic antagonist, propranolol, resulted in the development of less active tension by aortic smooth muscle from CA rats than from controls. Similar results were observed with the weakly alpha 1-adrenergic agonistic activities of tyramine, clonidine, and high concentrations of isoproterenol (10(-6)-10(-4) M). There was also a significant reduction in the tension developed by smooth muscles of the aortas from CA rats when depolarized with KCl in concentrations ranging from 8 to 20 mM. In contrast, aortic smooth muscle, contracted to 75% of maximum with KCl, showed an enhanced relaxation to the beta-adrenergic agonist, isoproterenol, in CA rats. These studies suggest that acclimation of rats to cold results in both a decrease in alpha-adrenergic responsiveness and an increase in beta-adrenergic responsiveness in vascular smooth muscle as well as a change in the biochemical events that couple activation of adrenergic receptors to changes in vasomotor tone.

Acclimatization↗
PubMed1983

Altered peripheral responsiveness to beta-adrenergic stimulation in experimental renal hypertension.

Hypertension, induced in male rats by encapsulation of both kidneys with latex envelopes, is associated with a reduction in maximal responsiveness to beta-adrenergic stimulation. Responsiveness was assessed by measurement of both water intake and plasma renin activity following acute subcutaneous administration of graded doses of isoproterenol, a beta-adrenergic agonist. At doses of isoproterenol in excess of 6 micrograms/kg body weight, s.c., the dipsogenic response of rats with renal hypertension was significantly (p less than 0.05) less than that of normotensive controls. Basal, unstimulated plasma renin activities were similar in both the normotensive and renal hypertensive groups. However, following administration of isoproterenol at doses of 5, 10, or 20 micrograms/kg body weight, s.c., plasma renin activity was elevated significantly (p less than 0.01) in the normotensive, but only in the lowest dose in the renal hypertensive group. These results suggest that maximal responsiveness to beta-adrenergic stimulation is reduced in the renal hypertensive rat; however, the mechanism(s) responsible for the reduced beta-adrenergic responsiveness remains speculative.

Animals↗
PubMed1983

Estimates of sodium and potassium intake.

Attempts have been made to estimate both the discretionary (consumer-controlled) and nondiscretionary (commercially controlled or naturally occurring) daily intakes of NaC1. These studies suggest that the average American has a total (discretionary plus nondiscretionary) daily intake of NaC1 ranging from 10 to 14.5 g, with about one third occurring naturally in food, one third added during food processing, and one third added by the consumer. Males consume more NaC1 than females and intakes of both sexes decline with age. Sodium chloride ingested with grain and cereal products and meat comprise about 50% of the daily nondiscretionary NaC1 intake. Additional amounts of sodium are ingested daily in drinking water and with drugs, but their contribution is difficult to determine. Total daily nondiscretionary intake of potassium is less well studied and is estimated to be in the range of 4 to 11 g/person.

Adolescent↗
PubMed1983

Effects of chronic administration of mestranol on alpha and beta adrenergic responsiveness in female rats.

Several alpha and beta adrenergic responses were studied in female rats after treatment with a low dose of the synthetic estrogen, mestranol (15 micrograms i.p. biweekly), for 4 to 6 weeks and compared with untreated controls. The response of blood pressure to exogenously administered norepinephrine was measured in conscious rats by means of an indwelling catheter in the femoral artery. Basal systolic blood pressure was not different between control and treated groups, or was any difference observed in peak systolic pressure after acute i.v. administration of l-norepinephrine in concentrations of 0.0625, 0.125, 0.250 and 0.625 micrograms. In contrast, the half-time of the blood pressure response was significantly prolonged after administration of the various concentrations of norepinephrine to mestranol-treated rats. The half-time of the pressor response observed in control animals administered 0.625 micrograms of norepinephrine was elicited in mestranol-treated animals by only 0.250 micrograms of norepinephrine. Analysis of the time course of the pressor response indicates that mestranol treatment altered the duration of the blood pressure increase without an apparent change in the onset of the pressor response. No differences between groups were observed in beta adrenergic responsiveness measured in terms of the isoproterenol-induced increase in either heart rate (beta-1 response) or water intake (beta-2 response). Finally, the contractile response of aortic rings from mestranol-treated rats to both l-norepinephrine (10(-9) to 10(-5) M) and l-phenylephrine (10(-8) to 10(-4) M) was significantly less than that of aortic rings from control rats. These data indicate, therefore, that in vivo cardiovascular responsiveness to norepinephrine does not reflect the attenuated vascular reactivity of isolated aortic rings. Insofar as the dominant feature of the in vivo adrenergic response appears to be prolongation of pressor action, the present study suggests that processes involved in the inactivation of circulating norepinephrine may be altered by chronic treatment with a low-dose of mestranol.

Animals↗