Search PubMed⌕ Search

Biomedical subjects

J T Fitzsimons

Publications and source records attributed to J T Fitzsimons.

At least 55 records · Page 3Linked to original sources
PubMed1980

Increased sodium appetite in adrenalectomized or hypophysectomized rats after intracranial injections of renin or angiotensin II.

Rats given free access to food, water and 2.7% NaCl and injected with either renin or angiotensin II into the preoptic area showed an immediate increase in water intake followed by an increase in intake of 2.7% NaCl. The rats continued to drink the hypertonic NaCl solution throughout the test session of 18 h. Intracranial injections of the dipsogen, carbachol, caused thirst but no sodium appetite. Bilateral adrenalectomy had no effect on either the initial water intake or the delayed intake of NaCl that was induced by intracranial injections of renin or angiotensin II. However, the increased water intake during the 18 h after the administration of renin was reduced to normal levels in adrenalectomized rats. Similar results were obtained with hypophysectomized rats. These results demonstrated that the delayed sodium appetite induced by renin or angiotensin II is not secondary to the stimulation of release of hormones from the pituitary gland or adrenal cortex.

Adrenalectomy↗
PubMed1980

Angiotensin in the control of water and sodium intake.

Angiotensin is the most potent naturally occurring substance known to produce normal and specific behavior patterns when injected into the brain. These actions of angiotensin on thirst and sodium appetite, when considered with its other actions, show that the hormone is intimately concerned in extracellular fluid volume control. The extent of the participation of angiotensin from various sources in the two behaviors remains uncertain since there are certainly other controls of thirst and sodium appetite that do not depend on angiotensin.

Angiotensins↗
PubMed1979

Short-latency drinking and increased Na appetite after intracerebral microinjections of NGF in rats.

NERVE GROWTH FACTOR (NGF) is a polypeptide trophic factor for peripheral sympathetic and sensory neurones(1,2). Apparent NGF(3-5) and NGF receptors(6,7) have also been identified in the brain, and intracerebral administration of NGF in the adult rat produces marked biochemical(8) and morphologica(9,10) changes in brain tissue. These findings, taken together with the observations that central injections of NGF facilitate behavioural recovery from brain damage(11,12), indicate that this polypeptide may have an important role in brain function. It has been observed that rats given intraventricular injections of up to 2.3 microg NGF drink copiously (M.E.L. and G. Guroff, unpublished observations). Perkins et al.(13) reported that diencephalic application of crystalline NGF (1-15 microg) resulted in an intense polydipsia. The present report confirms the observations of M.E.L. and Guroff, and extends the findings of Perkins et al.(13) by using solutions of NGF instead of crystals. It also describes for the first time a second phenomenon produced by intracranial administration of NGF, namely an intense appetite for aversive concentrations of sodium solutions.

Journal Article↗
PubMed1979

Dependence of spontaneous and angiotensin-induced drinking in the rat upon the oestrous cycle and ovarian hormones.

The influence of the oestrous cycle on spontaneous and dipsogen-induced drinking was studied in female rats. Spontaneous fluid intake was lowest on the day of oestrus. Drinking induced by subcutaneous isoprenaline, and by angiotensin II (injected into the preoptic area), also showed marked cyclical variation, being lower at pro-oestrus and oestrus than at other stages of the cycle. Drinking induced by subcutaneous hypertonic NaCl or by intracranial carbachol did not vary with the oestrous cycle. Cyclicity of spontaneous and of angiotensin-induced water intake was not apparent in rats before puberty or after ovariectomy. Ovariectomy reduced drinking in response to isoprenaline. Treatment with oestradiol benzoate (20 micrograms) caused a reduction in spontaneous water intake, but a marked increase in the drinking response to isoprenaline. Treatment with oestradiol benzoate and progesterone (2.5 mg) caused a larger decrease in spontaneous water intake and an insignificant increase in isoprenaline-induced drinking. Water intake induced by subcutaneous hypertonic saline was unaffected by gonadal steroids. The results provide further evidence for the view that the thirst of extracellular origin, in which the renin-angiotensin system is involved, is brought about by mechanisms different from those that respond to cellular dehydration. Only drinking caused by activation of extracellular mechanisms appeared to be sensitive to the ovarian cycle and to ovarian hormones.

Angiotensin II↗
PubMed1978

Petide antagonists of the renin-angiotensin system in the characterisation of receptors for angiotensin-induced drinking.

The two naturally occurring analogues of angiotensin II (AII), Asp1-Val5-AII and Asp1-Ile5-AII, were equally effective as intracranial dipsogens in the water-replete rat. Renin, synthetic tetradecapeptide renin substrate (SRS) and angiotensin I (AI) also produced copious drinking when injected into the brain, but the naturally occurring renin substrate of rat caused little drinking and was much less effective than SRS. Prior intracranial injection of pepstatin, a competitive antagonist of the renin-angiotensinogen reaction, reduced drinking in response to renin and SRS but not to AI and AII. Renin-, SRS- and AI-induced drinking were inhibited by the converting enzyme inhibitor SQ 20881 injected through the same intracranial cannula in antagonist to agonist ratio of 1000:1, whereas the AII response was enhanced, although not significantly so, and the carbachol response was unaffected. Finally, position 8 aliphatic substituted analogues of AII were competitive antagonists of AII-induced drinking, and also inhibited drinking induced by renin, SRS and AI injected through the same intracranial cannula, but they did not inhibit carbachol-induced drinking. In conclusion, the angiotensin-sensitive receptor for thirst does not accept SRS or AI. It responds best to AII.

Angiotensin II↗
PubMed1978

Eledoisin, substance P and related peptides: intracranial dipsogens in the pigeon and antidipsogens in the rat.

The undecapeptide eledoisin caused vigorous and copious drinking within a minute or two of injection into the pigeon forebrain. Systemic injections of the same doses were ineffective. The relative efficacy of eledoisin and angiotensin II as dipsogens in the pigeon was similar to that of carbachol and angiotensin II in the rat. The related peptides eledoisin hexapeptide, physalaemin and substance P also caused some drinking, but they were less effective than eledoisin. In the rat none of these substances caused drinking. On the contrary eledoisin and substance P were found to depress angiotensin-induced drinking, but carbachol-induced drinking was not depressed to the same extent by these peptides. The preferential depression of angiotensin II-induced drinking resembles the effects of other vasoplegic drugs on this response in the rat, and may be related to the potent vasodilator properties of these peptides.

Angiotensin II↗
PubMed1978

The renin-angiotensin system and sodium appetite.

1. Bilateral nephrectomy or bilateral ureteric ligation greatly reduced the intake and retention of sodium in sodium-depleted adrenalectomized rats which were experienced at drinking aversive concentrations of saline and which otherwise would have drunk and retained substantial quantities of sodium.2. Pharmacological activation of the renin-angiotensin system with isoprenaline or phentolamine caused increased intake of water but did not stimulate sodium appetite in sodium-replete adrenalectomized rats, and decreased sodium appetite in sodium-depleted adrenalectomized animals.3. Neither I.P. injections of renin nor intravenous infusions of angiotensin II stimulated sodium appetite in normal rats or sodium-replete adrenalectomized rats.4. No differences were found in the saline preference-aversion curves of normal rats not maintained on saline given intracranial injections of angiotensin II or carbachol.5. Preoptic injections of renin, renin substrate or angiotensin II into sodium-replete adrenalectomized rats which were maintained on water and 2.7% saline induced immediate thirst followed by some saline intake. The saline intake was markedly less than the spontaneous saline intake of the same rats when sodium depleted.6. Similar preoptic injections in sodium-depleted adrenalectomized rats caused increased water intake but did not increase the saline intake any further.7. Intracranial injections of carbachol had little effect on saline intake in either sodium-replete or sodium-depleted adrenalectomized rats but caused increased water intake.8. In conclusion, peripheral activation of the renin-angiotensin system stimulates water intake but has no direct effect on sodium appetite. Secondly, central administration of components of the renin-angiotensin system causes thirst and does not inhibit sodium appetite whereas centrally administered carbachol causes thirst and inhibits sodium appetite. Therefore the renin-angiotensin system has only a minor role in sodium appetite.

Adrenalectomy↗
PubMed1978

Drinking and haemodynamic changes induced in the dog by intracranial injection of components of the renin-angiotensin system.

1. Intracranial injections of the individual components of the renin-angiotensin system caused drinking in water-replete dogs. 2. Angiotensin II was the most reliable, potent and rapidly acting intracranial dipsogen and elicited drinking in the absence of peripheral circulatory changes. After the highest dose of angiotensin II (10(-9) mole) five dogs drank a mean amount of 380.0 +/- 88.6 ml. For the other components, the order of dipsogenic effectiveness was angiotensin I, synthetic renin substrate, and angiotensin III. 3. Isotonic saline, bradykinin (10(-10) mole), eledosin-hexapeptide (10(-10) mole), oxytocin (10(-10) mole) and prostaglandin F2alpha (1-200 X 10(-12) mole) were ineffective. 4. Intracranial renin (10 m-u.) produced a mean intake of 445 +/- 152 ml. of water in eight dogs. 5. Dog renin substrate and synthetic renin substrate, injected intracranially in a dose of 10(-10) mole, produced similar intakes of water but these amounts were very much less than the volume drunk in response to the same dose of angiotensin II. 6. None of the components injected into dipsogenically responsive sites in the brain caused changes in blood pressure, although the act of drinking itself produced a small rise. 7. Angiotensin II at the highest dose produced drinking when injected into the subfornical organ, preoptic region, anterior hypothalamus, lateral ventricle, third ventricle, ventral hippocampus and mid-line thalamus. Negative sites were found in the caudate nucleus, fourth ventricle, mid-brain, posterior thalamus, dorsal hippocampus, lateral hypothalamus and posterior hypothalamus. 8. After the lowest dose of intracranial angiotensin II (10(-12) mole) only the preoptic region and subfornical orgal were responsive. These two sites were equally sensitive in terms of latency and amounts drunk at all doses injected. 9. Angiotensin did not necessarily have to reach a cerebral ventricle in order to cause drinking. 10. The dog resembles the rat in its responsiveness to the dipsogenic action of intracranial angiotensin II. The regions of the brain from which drinking can be elicited are more widespread than has been claimed by some in the rat.

Angiotensinogen↗
PubMed1978

Systemic angiotensin-induced drinking in the dog: a physiological phenomenon.

1. Intravenous infusion of the individual components of the renin-angiotensin system caused drinking in dogs in water balance. 2. Angiotensin II was the most potent and rapidly acting peptide inducing drinking. The minimum effective rate of infusion was between 8.3 and 16.6 X 10(-12) mole kg-1 min-1 which yield blood levels of angiotensin II that fell well within physiological limits for the dog and were mildly pressor. Angiotensin I and synthetic renin substrate caused less drinking than angiotensin II, and angiotensin III was the least effective dipsogen. 3. Renin caused significant drinking when infused I.V. at a rate of 0.5 u. min-1 for 15 min. Drinking was slower in onset and continued for longer than after other components of the renin-angiotensin system. 4. Within the dose range 1875-15,000 X 10(-12) mole of angiotensin II the amount of water drunk depended more on the rate of infusion than on the duration of the infusion. 5. During an I.V. infusion of angiotensin II lasting 2 hr, the rate of drinking was greatest during the first 15 min. After this declined progressively. 6. A delay of 1 hr after the start of an intravenous infusion of angiotensin II before access to water was allowed, did not significantly reduce the amount of water drunk. Nor did infusion of isotonic saline for 105 min reduce drinking in response to a subsequent infusion of angiotensin II. However, a preload of dilute milk approximately equal in volume to the amount of water normally drunk in response to I.V. angiotensin II significantly reduced drinking. Therefore the dog stopped drinking during long-term infusions of angiotensin II owing to the action of satiety mechanisms and not to tachyphylaxis or fatigue. 7. Intracarotid infusion of angiotensin II, angiotensin I, synthetic renin substrate and angiotensin III, at 40 X 10(-12) mole min-1 also caused drinking. Intakes of water were similar to the intakes after I.V. infusion at six times the arterial rate, except that angiotensin I was relatively less effective by intracarotid infusion than by I.V. infusion. 8. Renin, infused at 0.5 u. min-1 for 15 min, was much less effective by intracarotid infusion than by intravenous. 9. These results are compatible with a role for circulating angiotensin II in the thirst of hypovolaemia or moderate extracellular dehydration.

Angiotensin II↗
PubMed1978

Angiotensin, thirst, and sodium appetite: retrospect and prospect.

The fact that drinking in response to some hypovolemic stimuli was attenuated by nephrectomy but not by ureteric ligation led to the suggestion that the renal renin-angiotensin system may play a role in hypovolemic thirst. The isolation of a thirst factor from the kidney and the demonstration that this substance was renin supported the hypothesis. Subsequently, it was shown that the effects of renin on drinking were mediated through angiotensin II, which proved to be a potent dipsogenic substance when administered systemically or injected directly into the brain. Recently, it has been shown that angiotensin II, infused intravenously or through the carotid artery at rates that produce increases in plasma angiotensin II levels similar to those that occur in mild sodium depletion, causes the water-replete animal to drink. This discovery establishes that angiotensin is a physiological stimulus to drinking but it leaves open the question of the extent of the involvement of renal renin in normal thirst. Other unsolved problems are the role of cerebral isorenin in angiotensin thirst and its relationship with renal renin, and in view of its stimulating action on sodium intake when infused into the brain, whether angiotensin plays a significant role in sodium appetite.

Angiotensins↗
PubMed1977

Lipogenesis in hepatocytes of genetically obese rats.

A simple method for the preparation of hepatocytes in good yield from obese rats is described. Lipogenesis from [U-14C]-lactate, [U-14C]-glucose and tritiated water has been investigated in hepatocytes prepared from both genetically obese 'fatty' rats and their lean littermates. Hepatocytes from obese rats demonstrate elevated rates of fatty acid and sterol synthesis in contrast to hepatocytes from lean animals. The rate of fatty acid synthesis is sensitive to the dietary status of the animal prior to preparation. The enhanced lipogenesis in hepatocytes from obese rate depends on lactate as a source of carbon rather than glucose. The role of the liver in genetic obesity is discussed with particular reference to the major precursor for hepatic lipogenesis.

Animals↗