Biomedical subjects

D A Denton

Publications and source records attributed to D A Denton.

At least 55 records · Page 3Linked to original sources

PubMed1992

Effect of CRF, ACTH and adrenal steroids on sodium intake and excretion of rabbits.

The effect of CRF, ACTH and adrenal steroid hormones on the sodium intake and excretion of wild and laboratory rabbits was studied in our laboratory in detail. All these hormones are known to play important roles in the initiation and maintenance of stress-reaction. Intracerebroventricular (icv) infusion of CRF increased both sodium intake and excretion of rabbits on the day of the infusion, and the stimulated sodium turnover persisted for several days after the infusion stopped. Systemic administration of the same dose of CRF did not influence sodium intake or excretion. Icv infusion of CRF was accompanied by a rise in plasma cortisol and plasma corticosterone concentration. Plasma sodium concentration was unchanged despite the increased turnover. The elevated plasma concentration of adrenal steroid hormones indicates that icv infused CRF resulted in ACTH and consequent cortisol and corticosterone release. Earlier studies in our laboratory established that ACTH, and similarly cortisol and corticosterone, when injected systemically, also elicited increased sodium intake, which was accompanied by increased sodium excretion. The rise in sodium turnover occurred on the second or third day of ACTH or steroid administration. The difference in the time of onset of sodium appetite between icv CRF and ACTH or adrenal steroids indicates that CRF influences sodium intake by other mechanisms as well. These other contributing mechanisms are probably activated by the binding of CRF to the specific binding sites demonstrated earlier in the rabbit's brain. Its is possible, that the small natriuresis accompanying icv infusion of CRF has some role in the initiation of the sodium appetite.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

PubMed1991

Central administration of somatostatin suppresses the stimulated sodium intake of sheep.

The effect of intracerebroventricular (i.c.v.) infusion (50 micrograms/h over 3 h) of somatostatin (SOM) on Na and water intake of sheep was determined. In Na-deplete sheep, infusion of SOM-(28) but not SOM-(14) decreased (P less than 0.05) Na intake, while both SOM-(28) and SOM-(14) increased water intake. I.c.v. infusion of SOM-(28) did not significantly affect Na or water intake of Na-replete sheep. I.c.v. infusion of SOM-(28) decreased (P less than 0.01) Na intake but did not alter the high water intakes of water-deprived sheep or sheep infused i.c.v. with angiotensin II. The results are compatible with an inhibitory action of somatostatin on stimulated brain mechanisms subserving Na appetite but not on stimulated brain mechanisms subserving thirst. Somatostatin may antagonize the inhibition of thirst in Na-deplete sheep. The results suggest that somatostatin may have a regulatory role in ingestive behavior concerned with body fluid and Na homeostasis. The difference between SOM-(14) and SOM-(28) in decreasing the Na intake of Na-deplete sheep may be due to a difference in potency or mechanism of action.

Angiotensin II↗

PubMed1991

Corticotropin-releasing factor enhances sodium and water intake/excretion in rabbits.

Sodium and water intake and excretion of wild rabbits was studied during intracerebroventricular (icv) infusion of corticotropin-releasing factor (CRF). Icv infusion of 200 and 600 pmol/h for 22 h induced changes in the ingestive and general behavior of animals. Increased consumption of 0.5 M NaCl solution was observed during the day of infusion, accompanied by increased sodium excretion, and food intake was decreased. The rabbits maintained the high sodium turnover, together with a high water turnover, for 2-3 days after the icv infusion stopped. Icv infusion of CRF induced strange behaviour in wild rabbits, they appeared to react with fright to normal daily events around them. The strange behaviour started about two hours after the beginning of icv infusion and disappeared immediately after the infusion stopped. On the basis of present and earlier observations, that systemic administration of adrenocorticotropin (ACTH) and adrenal steroid hormones induce increased sodium turnover, it is proposed that changes in the sodium and water metabolism might constitute part of the general stress reaction of the body.

Animals↗

PubMed1991

Sodium/water intake of rabbits following administration of hormones of stress.

Intracerebroventricular (ICV) infusion of CRF, for 22 h, induced five- to seven-fold increase in the daily intake of sodium chloride solution in wild rabbits. The increased sodium intake persisted for 3 days after the infusion stopped and was accompanied by increased sodium excretion, water turnover and decreased food intake. ICV infusion of CRF also induced a change in the general behaviour of the animals, which lasted throughout the infusion only. Systemic, but not ICV administration of ACTH, similar to systemic administration of adrenal steroid hormones (demonstrated in earlier studies), induced gradual increases in the daily sodium intake and excretion of rabbits, as did restraint by tight jackets. The increased sodium intake was accompanied by increased sodium excretion and water turnover, and lasted as long as the administration of hormones. Together these results lead to the hypothesis that increased sodium intake might be an integral part of the stress reaction of the body and not the consequence of distortions of other regulatory functions.

Adrenocorticotropic Hormone↗

PubMed1990

Subfornical organ lesion decreases sodium appetite in the sodium-depleted rat.

The effect of subfornical organ (SFO) lesion on various models of ingestive behaviour was investigated in rats. Intake of water after 24 h water deprivation or systemic administration of hypertonic NaCl were not altered by SFO lesions. Intake of food or water after 24 h of food deprivation were not altered by SFO lesions. Intake of NaCl after furosemide-induced Na depletion was decreased by ablation of the SFO. This decrease in Na intake was ameliorated by pretreatment with a low dose of captopril. These results suggest that the SFO is involved in Na intake after Na depletion, but not in water or food intake following periods of water or food deprivation, respectively. The observation that a low dose of captopril can eliminate the decrease in Na appetite which occurred subsequent to SFO lesion suggests that other brain areas may also participate in Na-depletion-induced Na appetite.

Animals↗

PubMed1990

Opening the blood-brain barrier to zinc.

Sheep with guide tubes implanted over the brain lateral ventricles, in order to facilitate episodic sampling of cerebrospinal fluid (CSF), were used to determine the effects of increasing cranial blood osmolality or electroconvulsive shock (ECS) on the permeability of the blood-brain barrier (BBB) to zinc. Zinc acetate solution (1 mg Zn/ml) was infused intravenously (i.v.) at 1.0 ml/min for 30 min and then continuously at 0.125 ml/min. This infusion increased plasma total zinc concentration (pZn) approximately 10-fold without altering CSF zinc concentration (CSFZn). After 1.5-3.5 h, 4 M NaCl was infused at 5-10 ml/min for 10 min into one carotid artery with the other carotid artery occluded, or the animals were anaesthetized and given an ECS (140 V, 2 s). Paired samples of blood and CSF were collected before and after these treatments. Results were: (i) CSFZn was approximately one tenth of pZn; (ii) zinc administered i.v. was almost completely excluded from the CSF; (iii) increased cranial blood osmolality or ECS increased CSFZn in all experiments, but the time course and extent of the rise were variable. CSFZn reached the concentrations of zinc in normal sheep plasma in some experiments; (iv) CSFZn subsequently fell towards the low values of zinc in normal CSF; (v) the animals suffered no evident ill-effects from either procedure. The procedures may, therefore, be used for reversible opening of the BBB to particles such as zinc in conscious or anaesthetized sheep with no troublesome sequelae.

Animals↗

PubMed1990

Sodium and water intake of sheep, rabbits and cattle during ICV infusion of eledoisin.

The present study reports the effects of ICV administered eledoisin, the most potent anti/dipsogenic member of the tachykinin family, in three species. Sheep with chronic parotid fistula lost daily 200-400 mmol sodium in 3-4 l of saliva. During ICV infusion of eledoisin, 2 to 50 ng/min, a decrease in sodium intake was observed. If water was withheld for 22 hours, sheep normally drank 5.4 l water on presentation. During ICV infusion of eledoisin, 50 ng/min, water intake increased significantly. Wild rabbits lost 5 mmol sodium in 50 ml of urine after injection of furosemide. During ICV infusion of eledoisin, 30 ng/min, a decrease in sodium intake and an increase in water drinking was observed. Cows prepared with parotid fistula had access to sodium solution every other day to replace salivary sodium loss. During ICV infusion of eledoisin, 50 and 150 ng/min, a decrease in sodium intake occurred, and water intake was unaffected. These results confirm that central administration of eledoisin specifically influences ingestive behaviour in mammals and draws attention to some species differences in the observed effects.

Animals↗

PubMed1990

Angiotensin and salt appetite of BALB/c mice.

The influence of systemic or intracerebroventricular (icv) administration of angiotensin II on the intakes of NaCl solution, water, and food was investigated in BALB/c mice. Systemic administration of angiotensin II had little, if any, influence on these ingestive behaviors. On the other hand, icv infusion of angiotensin II at 70 ng/day increased (P less than 0.05) intakes of NaCl solution and water by the third day of infusion. The amount of NaCl ingested daily during the infusion was two to three times body sodium content. The mean daily water intake increased to 40-60% of body weight. The vast increase in NaCl intake was not secondary to a natriuresis caused by the icv infusion of angiotensin II. The results suggest that angiotensin II has a direct effect on neural systems involved in sodium appetite in this species.

Angiotensin II↗

PubMed1990

Effect of angiotensin-converting enzyme inhibitor on salt appetite and thirst of BALB/c mice.

The role of angiotensin II (ANG II) in Na-depletion-induced Na appetite of mice was investigated. Intraperitoneal injection of the angiotensin-converting enzyme inhibitor captopril at 1.7 mg/mouse (high dose) decreased the Na intake of the Na-depleted (furosemide-treated) mice by 80-85%. The decrease in Na intake was restored to the initial level by concurrent subcutaneous infusion of ANG II. High dose of captopril also decreased the Na intake of fluid-deprived, Na-depleted mice. High dose of captopril did not alter water intake in any of the four conditions examined, i.e., in fluid-replete, Na-depleted, water-deprived, or fluid-deprived, Na-depleted mice. Low dose of captopril (1.7 microgram/mouse) tended to or significantly enhanced Na intake of Na-depleted mice. Low dose of captopril, however, did not enhance water intake in any of the conditions examined. Both high- and low-dose captopril treatment decreased food intake in water-deprived mice, whether or not the mice were Na depleted as well. The addition of captopril (0.1 or 1.0 mg/ml) to the drinking water did not influence Na or food intake. Water intake was enhanced during treatment with the low but not with the high dose of captopril. The results are consistent with the proposition that ANG II is involved in the Na appetite of Na-depleted mice. ANG II does not appear to have a role in water intake of Na-depleted or water-deprived mice, but neural mechanisms in which angiotensin has a role may influence food intake of water-deprived mice.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1990

Decreased cerebral sodium concentration and sodium appetite in BALB/c mice.

BALB/c mice were allowed free access to water, food, and 0.3 M NaCl. Intracerebroventricular infusion of 0.7 M mannitol in artificial cerebrospinal fluid (CSF) was used to reduce CSF sodium concentration. The infusion was made at 24 microliters/day, which was similar on a body weight basis to the rate that evoked a large increase in sodium appetite in sheep. Reduction of CSF sodium concentration did not increase the voluntary sodium intake of sodium-replete mice or furosemide-treated, sodium-depleted mice. Thus, in contrast to findings in sheep and cattle and similar to the findings in the laboratory rat and wild rabbits, changes in cerebral sodium concentration are apparently not involved in the sodium appetite of mice.

Animals↗

PubMed1989

Cerebral sodium sensors in the sodium-deplete sheep.

The sodium intake of sodium deplete sheep was studied during local, push-pull perfusion of different solutions within the third cerebral ventricle. Sheep were made sodium deplete by continuous loss of parotid saliva, and were allowed access to 0.6 M NaHCO3 solution for 2 h daily. Local perfusion within the third cerebral ventricle was performed before and during the access to sodium solution. Four perfusion sites were used: anterior dorsal and ventral, and posterior dorsal and ventral. Perfusion of 200 mM Na-csf caused a decrease in sodium intake at each perfusion site. Perfusion of ouabain, 10(-6) M, caused a reduction in sodium intake only during perfusions within the anterior portion of the third ventricle. The results may indicate that specific neuronal elements sensitive to changes in intracellular sodium concentration are located around the anterior portion of the third cerebral ventricle. These neurones, however, are not exclusive sites from where sodium intake of sodium deplete sheep can be influenced.

Animals↗

PubMed1989

Effect of varying the composition of CSF on urinary excretion in the conscious rat.

The effect of 4 h intracerebroventricular (i.c.v.) infusion of various solutions on the renal excretion of Na and K and urinary flow rate was examined in conscious unrestrained rats not water-loaded. I.c.v. infusion of iso- or hypo-osmotic solutions with low [Na] induced a diuresis but did not alter renal excretion of Na or K. I.c.v. infusion of hyperosmotic solutions with normal or elevated [Na] induced a natriuresis and kaliuresis. Hyperosmotic mannitol solutions caused a diuresis but hyperosmotic NaCl or sucrose solutions caused a diuresis only when the rats drank water and/or sodium solution during the infusion period. I.c.v. infusion of hyperosmotic NaCl but not hyperosmotic mannitol increased blood pressure. The results are consistent with the involvement of cerebral osmosensors in the control of urinary excretion of Na and K, and of cerebral Na sensors in the control of urinary flow rate. Increased blood pressure, as occurred during i.c.v. infusion of hyperosmotic NaCl, may also contribute to the increased excretion of Na and K.

Animals↗

PubMed1989

Intracerebroventricular saccharide infusions inhibit thirst induced by systemic hypertonicity.

The effect of intracerebroventricular (i.c.v.) infusion of various iso- and hypertonic saccharide solutions on water intake stimulated by intracarotid (i.c.) infusion of hypertonic NaCl was studied in sheep. Without an i.c.v. infusion, water intake during a 10-min period following an i.c. infusion of 4 M NaCl (1.4 ml/min over 20 min) was 1.5-2.0 litres. I.c.v. infusion of all saccharide solutions (made up in artificial cerebrospinal fluid (CSF) with no Na) tested, 0.27 or 0.7 M D-glucose, L-glucose, 2-deoxyglucose and sucrose, decreased (35-65%) water intake. In general, there was little or no difference in antidipsogenic effectiveness between the isotonic and the hypertonic solutions or between the different saccharides used. I.c.v. infusion of artificial CSF ([Na] = 150 mM) did not alter water intake. CSF [Na] was decreased by all of the saccharide infusions. CSF osmolality was increased by the hypertonic solutions, was decreased by the artificial CSF and was unchanged by the isotonic solutions infused. The observation that the antidipsogenic effectiveness of saccharides which readily cross the blood-brain barrier (BBB; D-glucose, 2-deoxyglucose) was similar to that of saccharides which do not readily cross the BBB (sucrose, L-glucose) contrasts with effects reported on sodium appetite and suggests that the Na sensors involved in the inhibition of hypertonic NaCl-stimulated water intake are located close to or on the surface of the brain ventricular system, i.e. are responsive to changes in CSF [Na].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Understanding the mechanism of adrenocortical steroid hypertension.

Studies of the mechanism of ACTH induced hypertension in sheep have led to the hypothesis that adrenocortical steroids may raise blood pressure by a "hypertensinogenic" action which can be distinguished from effects mediated by occupancy of classical mineralocorticoid or glucocorticoid receptors. This concept is supported by recent structure-activity studies using synthetic and naturally occurring steroids. Development of steroid hypertension is rapid (4-6 h) and although associated with an increase in cardiac output, changes in total peripheral resistance are important. Many different mechanisms have been proposed to explain how steroids raise blood pressure. In sheep it has been shown that the autonomic nervous system and vasoactive prostanoids appear to buffer, rather than cause, the rise in blood pressure. The renin-angiotensin system, AVP and serotonin are also unlikely to be involved. Further, the effects of steroids on blood pressure are not simply related to effects on Na status and changes in body fluid volumes. A direct involvement of the central nervous system remains to be established. In understanding how ACTH raises blood pressure, studies in sheep have shown that it is important to try and dissociate the effects of steroids involved in development of hypertension from the many other actions of steroids.

Adrenal Cortex Hormones↗

PubMed1989

Voluntary ethanol intake of individually- or pair-housed rats: effect of ACTH or dexamethasone treatment.

The effect of ACTH or dexamethasone treatment on ingestion of 10% ethanol, 0.5 M NaCl and water was studied in individually- and pair-housed rats. Crowding or decreasing the amount of space per rat by increasing the number of rats per cage from 1 to 2, together with the associated increase in social interactions caused a large increase in ethanol intake. In pair-housed rats and in rats housed alone, ACTH treatment caused a large increase in Na intake but no change in ethanol intake. In pair-housed rats and in rats housed alone, dexamethasone treatment caused no change in either ethanol or Na intake. Thus, it would appear that the induction or maintenance of a high ethanol intake of rats during crowding, a presumed social stressor, can not be attributed entirely to either an increase in blood ACTH levels with the subsequent increase in glucocorticoid hormones or to a decrease in blood ACTH and natural glucocorticoid hormone levels. However, the possibility that ACTH and/or adrenocorticoid hormones, combined with other physiological or environmental factors, causes stressor-induced ethanol intake cannot be excluded.

Adrenocorticotropic Hormone↗

PubMed1989

Adrenocortical steroid requirements for initiation of ACTH-dependent hypertension in sheep.

1. Previous studies demonstrated that the combined infusion of cortisol (F), aldosterone (ALDO), deoxycorticosterone (DOC), corticosterone (B), 11-deoxycortisol (S), 17 alpha-hydroxyprogesterone (17 alpha OHP) and 17 alpha, 20 alpha- dihydroxy-4-pregnane-3-one (17 alpha 20 alpha OHP), at rates equivalent to their production during adrenocorticotrophic hormone (ACTH) treatment, reproduced the pressor and metabolic responses to ACTH administration in sheep. 2. This study examined which of these adrenocortical steroids were necessary for the initiation of the hypertension produced by these steroids in sheep. 3. Infusion of F, ALDO, 17 alpha OHP and 17 alpha 20 alpha OHP together, increased MAP by 19 mmHg, similar to both complete steroid cocktail (+25 mmHg) or ACTH administration (+21 mmHg). Infusion of F, 17 alpha OHP and 17 alpha 20 alpha OHP increased MAP by +7 mmHg. Infusion of ALDO, 17 alpha OHP and 17 alpha 20 alpha OHP had no effect on MAP. Thus F and ALDO were essential for the pressor effects of the steroid infusion. 4. To determine the role of glucocorticoid activity in the MAP rise, prednisolone, a non-pressor glucocorticoid, was substituted for cortisol. Combined prednisolone, ALDO, 17 alpha OHP and 17 alpha 20 alpha OHP infusion did not raise blood pressure. This suggested that the mineralocorticoid component rather than glucocorticoid component of cortisol's activity was involved in the pressor response. 5. Aldosterone (7 micrograms/h) was substituted for cortisol, giving a total of 10 micrograms/h aldosterone. High dose ALDO (10 micrograms/h), 17 alpha OHP and 17 alpha 20 alpha OHP infusion raised blood pressure by 18 mmHg. Thus, the essential role of cortisol appeared to be due to its occupancy of mineralocorticoid receptors, rather than glucocorticoid receptors. 6. Given that ACTH produces a transient initial increase in aldosterone secretion of up to 10 micrograms/h, it appears that aldosterone and not cortisol is essential for the pressor effects of ACTH. 7. Hypertension resulting from the combined steroid infusion in the sheep appears to be produced by a mechanism which involves a complex interaction between ALDO, F, 17 alpha OHP and 17 alpha 20 alpha OHP. Therefore, the putative 'hypertensinogenic' receptor may be multivalent with binding sites for F, ALDO and 17 alpha 20 alpha OHP, or is a site of single interactive receptors for these steroids and that F exerts its permissive action by occupying the same site as ALDO on the hypertensinogenic receptors.

17-alpha-Hydroxyprogesterone↗

PubMed1989

Sodium appetite and thirst in cattle subjected to dehydration.

Cows having free access to water (hydrated) or deprived of water for 26.5 h (dehydrated) were infused for 3 h with angiotensin II or captopril solutions intravenously (iv) or intracerebroventricularly (icv) beginning 1 h before access to 0.3 M NaHCO3/NaCl solution for 2 h. The results agree with the results of the experiments with the same agents and doses in Na-deficient cows. Only iv infusion of angiotensin II stimulated Na appetite and only icv infusion of angiotensin II stimulated thirst. Therefore, barriers to the penetration of angiotensin II in the brain determined the particular site of action and elicited response. Dehydration did not stimulate Na appetite and, as shown previously, Na deficiency did not stimulate thirst, but both behaviors seem to be influenced by angiotensin-related mechanisms in the brain. The inability of iv angiotensin II to stimulate Na appetite in hydrated cows might be explained by the lack of a response caused by, and common to, Na deficiency and dehydration, e.g., upregulation of angiotensin II receptors, or reduced extracellular fluid volume.

Animals↗

PubMed1989

Recent studies of bone appetite in cattle.

Cows depleted of phosphorus by loss of saliva from a parotid fistula and low dietary phosphate developed an avid appetite for bones. The behaviour is innate and predominantly cued by olfactory stimuli. Meat, blood or fat were not attractive and bones became more attractive after aging for 1.5-2.0 years. The appetite was also shown for guano-derived rock phosphate and bird excreta. There was no interest in inorganic calcium and phosphate salts or ashed bone. The attractant is therefore an organic constituent of aging bone and was found to be at highest concentration in the marrow fraction. Water, ether and vacuum distillation extracts of old bone or marrow, added to unattractive materials e.g., ashed bone, rendered them attractive. The residues of such extraction were of diminished interest. The attractiveness of the fractionated extracts was highest in the neutral fraction. The bone appetite was abolished by increasing the phosphate concentration in plasma but not in cerebrospinal fluid. The phosphate concentration in the blood appears, therefore, to regulate the bone appetite. The sensors could be in brain regions without a blood-brain barrier. Chronic severe phosphorus deficiency was associated with bone resorption, reduced osteoblastic and hemopoietic activities, and abnormal blood progesterone cycles.

Animals↗