Search PubMed⌕ Search

Biomedical subjects

J T Fitzsimons

Publications and source records attributed to J T Fitzsimons.

At least 19 recordsLinked to original sources
PubMed1992

Intracerebroventricular angiotensin II-induced thirst and sodium appetite in rat are blocked by the AT1 receptor antagonist, Losartan (DuP 753), but not by the AT2 antagonist, CGP 42112B.

In the rat, intakes of water and 1.8% NaCl induced by I.C.V. angiotensin II were inhibited by prior I.C.V. injection of the angiotensin subtype 1 receptor antagonist, Losartan, but not by the subtype 2 receptor antagonist, CGP 42112B. Drinking induced by I.C.V. carbachol was unaffected by either antagonist.

Angiotensin II↗
PubMed1989

Effects of soyabean and ascorbic acid on experimental carcinogenesis.

1. Ultrastructural changes in liver tissue of mice fed nitrosamine precursors, dibutylamine and nitrite, were observed. 2. The protective effect of soyabean in a diet containing nitrosamine precursors was demonstrated. 3. Liver tissue was examined to investigate the anticarcinogenicity of ascorbic acid. 4. The significance of soyabean and ascrobic acid in counteracting the potential hazards due to nitrosamine precursors is discussed.

Animals↗
PubMed1988

Thirst in Brattleboro rats.

Thirst mechanisms in Brattleboro rats are activated because of a deficiency in circulating vasopressin. Plasma osmolality, renin, and angiotensin II (ANG II) are increased. We measured the responsiveness of Brattleboro rats and appropriate control strains to cellular and extracellular thirst stimuli taking the spontaneous base-line water intake into account. Brattleboro rats drank more in response to intraperitoneal hypertonic NaCl than controls, but when their fluid losses were prevented by nephrectomy they did not overdrink. Despite low urinary concentration, Brattleboro rats excreted the sodium load at least as rapidly as the controls. Brattleboro rats drank after intracranial injection of renin, renin substrate, and ANG I and II. The dose-response curves were similar to controls, although the Nottingham Long-Evans control strain drank significantly less in response to some doses of the peptides. Intracranial captopril inhibited renin- and ANG I-induced but not ANG II-induced drinking. Isoproterenol reduced spontaneous drinking of Brattleboro rats but increased drinking in controls. However, when urinary losses were prevented by ureteric ligation, isoproterenol caused markedly greater water intake in Brattleboro rats than in controls. Subcutaneous captopril in moderate, thirst-enhancing doses also caused a larger increase in water intake in Brattleboro rats than in controls. Therefore the renin-angiotensin system of Brattleboro rats is more responsive to renin-dependent thirst challenges than that of normal controls.

Angiotensin I↗
PubMed1985

Structural effects of external media on isolated myelinated axons.

Myelinated axons were isolated from the sciatic nerve of Xenopus laevis by desheathing and teasing, and were mounted for short-term light microscope observation in different media. Fibres mounted in a conventional physiological saline showed a tendency to gross structural changes, including collapse of axons and separation of the axon from the myelin sheath. With isotonic media based on 120mM potassium aspartate, or 120mM potassium glutamate, structural stability and axoplasmic function (assessed by persistence of particle transport) were well maintained. The speeds of retrograde particle transport in fibres immersed in potassium aspartate or potassium glutamate medium ranged from 0.05 to 3.15 micron/sec with mean speeds of 1.05 and 1.2 micron/sec. Transport persisted for up to 3 hr. Isotonic media based on amino acids but lacking K+ or Na+ were unsatisfactory short-term culture media and destabilized myelin structure. Inclusion of 60 mM KCl in the medium reduced structural disruption and allowed particle transport to persist.

Animals↗
PubMed1985

Effects of angiotensin or carbachol on sodium intake and excretion in adrenalectomized or deoxycorticosterone-treated rats.

In adrenalectomized, deoxycorticosterone-treated and normal rats, injection of angiotensin II through a cannula implanted in the preoptic region caused increased intakes of hypertonic NaCl and water when both fluids were available, whereas injection of carbachol through the same cannula only caused increased water intake. Carbachol depressed NaCl intake of adrenalectomized rats that were allowed access to hypertonic NaCl after being deprived of it for 24 h. Angiotensin-stimulated rats were more likely to go into positive sodium balance than controls, whereas carbachol-stimulated animals were more likely to go into negative balance. After angiotensin, adrenalectomized or deoxycorticosterone-treated rats drank a larger proportion of their total fluid intake as hypertonic NaCl than did normal rats. Angiotensin caused significant increases in sodium excretion in normal, isotonic saline-loaded and deoxycorticosterone-treated rats, but not in adrenalectomized rats, although angiotensin caused increased intakes of NaCl in all groups. On the other hand, carbachol caused a significant increase in sodium excretion at 1 h in all groups despite the absence of an increase in NaCl intake. After angiotensin, only normal rats showed a significant kaliuresis at 1 h, whereas all carbachol-injected rats showed increased potassium excretion. Therefore, angiotensin is a primary stimulus to increased sodium appetite, normally acting in conjunction with other stimuli which enhance its effect, whereas carbachol is a central inhibitor of sodium appetite.

Adrenalectomy↗
PubMed1985

The effect of captopril on sodium appetite in adrenalectomized and deoxycorticosterone-treated rats.

Captopril caused a renin-dependent increase in water intake in rats with bilateral ureteric ligation. But despite the fluid retention and fall in osmolality caused by the increased water intake, rats with ureteric ligation did not drink the 2.7% NaCl also offered to them. In rats with a pre-existing increase in sodium appetite caused by adrenalectomy, low dosage of captopril augmented intake of both water and 2.7% NaCl whereas high dosage inhibited intake of both fluids after an initial increase in water intake. In contrast, rats with a pre-existing increase in sodium appetite caused by daily injections of deoxycorticosterone showed no changes in intake of water or 2.7% NaCl after either low or high dosage of captopril, though they drank both fluids after intracranial injection of angiotensin II. Increases in water and 2.7% NaCl intake caused by low dosage of captopril in adrenalectomized rats were not secondary to increased urinary fluid and electrolyte losses. Decreases in intake after high dosage were not explained by the rats being too weak to drink. Low and high dosage of captopril caused increases in plasma renin concentration in adrenalectomized rats, but in contrast renin remained undetectable in the plasma of deoxycorticosterone-treated rats after the highest dosage of captopril. Whether or not captopril affected a pre-existing sodium appetite depended on whether or not it increased plasma renin. Since it affected the pre-existing sodium appetite and plasma renin in the adrenalectomized rat but neither of these in the deoxycorticosterone-treated rat, it is likely that the appetite was renin-dependent in the former but not in the latter. Because captopril only affected thirst in the rat with ligated ureters whereas it affected both sodium appetite and thirst in the adrenalectomized rat, increases in renal renin secretion alone may not be enough to stimulate sodium appetite. The additional stimulus provided by adrenalectomy, or the absence of some inhibitory factor that may be present after ureteric ligation, is also needed.

Adrenalectomy↗
PubMed1984

Increased sodium appetite and polydipsia induced by partial aortic occlusion in the rat.

Partly occluding the abdominal aorta between the renal arteries caused the rat to drink steadily increasing amounts of 2.7% NaCl when this solution and water were available. The increase in NaCl intake preceded the increase in water intake that also occurred after aortic occlusion, and intakes of both fluids were reaching maximal values 1-2 weeks after operation. The amounts of fluid drunk during the day increased greatly. This change in the pattern of drinking, together with the rise in fluid intake and the drop in food intake meant that drinking was less associated with feeding than it is in the normal rat. The rats went into fluid and electrolyte deficit within 24 h of partial aortic occlusion and remained in deficit for about a week (the duration of the balance experiment) despite increasing intakes of NaCl and water. Renal function was unimpaired during the first 2 weeks, and the abnormal signs were mainly and rapidly reversed by removal of the ischaemic kidney or administration of the angiotensin converting enzyme inhibitor, captopril. Therefore polydipsia and increased sodium appetite in the first 2 weeks after aortic occlusion were likely to have been caused by fluid deficit, with increased renin secretion from the ischaemic kidney contributing to both behaviours. Arterial blood pressure rose immediately after aortic occlusion, before the onset of increased drinking. Up to 3 weeks after operation the incidence and severity of the hypertension did not appear to depend on the spontaneous changes in intake of water or hypertonic NaCl.

Animals↗
PubMed1984

Involvement of the renin-angiotensin system in captopril-induced sodium appetite in the rat.

The angiotensin converting enzyme inhibitor, captopril, given to rats in their drinking water (about 40 mg/day) for 6 days caused an increase in intake of hypertonic NaCl solution which began 1-2 days after the captopril was started and reached a plateau after 4-5 days. Twice-daily subcutaneous injections of captopril (15 mg per injection) elicited a sodium appetite similar in pattern to that seen with oral administration. The rats remained in sodium and fluid balance during oral captopril treatment and the haematocrit did not alter. Captopril infused directly into the ventricles (12 micrograms/h), or captopril reaching the brain from the periphery across a leaky blood-brain barrier, suppressed the sodium appetite which normally follows oral captopril. Continuous intravenous infusion of captopril at rates high enough to block angiotensin converting enzyme in the brain (25, 50 or 500 mg/day) did not cause sodium appetite. As soon as the rate was reduced to a low value (5 mg/day), NaCl intake increased. In conclusion, moderate levels of circulating captopril which do not cross the blood-brain barrier in sufficient amounts to block cerebral angiotensin converting enzyme, result in an increase in circulating angiotensin I which stimulates sodium appetite when it is converted to angiotension II in the brain.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

The renin-angiotensin system and sodium appetite.

Intracranial renin is a potent stimulus to sodium appetite and thirst, the effects being mediated by local generation of angiotensin II. Intakes are persistent and lead to fluid retention during the first 24 h (Avrith and Fitzsimons, 1983). Increased circulating renin after captopril treatment in adrenalectomized rats (Elfont and Fitzsimons, 1981), or in renal hypertension following partial inter-renal aortic ligation (Costales et al., 1982), also leads to increased intakes of 2.7% NaCl and water. Fluid intakes after aortic ligation were independent of the severity of hypertension produced by this procedure. In both the examples given, additional stimulation resulting from the hypovolaemia itself is required for the full expression of increased sodium appetite, but in both cases angiotensin makes a significant contribution to sodium appetite as well as thirst. Therefore, as has been shown for thirst, angiotensin is one of a number of factors that act together to cause increased sodium appetite in hypovolaemia.

Adrenalectomy↗
PubMed1983

The effects of corticosterone, cold exposure and overfeeding with sucrose on brown adipose tissue of obese Zucker rats (fa/fa).

GDP binding to brown-adipose-tissue mitochondria was decreased in obese Zucker rats. Adrenalectomy restored both GDP binding and serum tri-iodothyronine of obese rats to values observed in lean rats. The effects of adrenalectomy on GDP binding and serum tri-iodothyronine were reversed by corticosterone. Decreasing food intake had no effect on brown-adipose-tissue GDP binding in obese rats. Young (5-week-old) obese rats showed a normal increase in brown-adipose-tissue mitochondrial GDP binding after housing at 4 degrees C for 7 days, but this response was attenuated in 10-week-old obese rats. Overfeeding with sucrose increased brown-adipose-tissue thermogenesis in lean, but not in obese, rats. After adrenalectomy, overfeeding with sucrose enhanced brown-adipose-tissue mitochondrial GDP binding in obese rats.

Adipose Tissue, Brown↗
PubMed1983

Em localization of atpase on microtubules of isolated cilia from Tetrahymena vorax.

1. Isolated cilia were prepared from Tetrahymena vorax using the local anaesthetic dibucaine in the deciliation step. 2. ATPase was cytochemically localized on microtubules of isolated cilia using the Washstein-Meisel incubation; deposition of lead phosphate indicated the sites of enzyme activity. 3. Mild fixation conditions gave optimum localizations. Satisfactory results were attained using 0.5% glutaraldehyde with a fixation time of 30 min. 4. An increase in ATPase activity, as judged by lead phosphate precipitation, was observed when cytochemical incubations were increased from 5 min to 1 hr. An incubation time of 15 min gave optimum results. 5. No advantage was gained with incubation times over 1 hr as diffusion of reaction product may occur. 6. No ATPase activity was observed in control incubations where the enzyme substrate ATP was omitted. 7. Purified cilia preparations provide useful starting material for the study of microtubular ATPase.

Adenosine Triphosphatases↗
PubMed1983

Renin-induced sodium appetite: effects on sodium balance and mediation by angiotensin in the rat.

1. Injection of pig renin or purified renin from the mouse submaxillary gland into the preoptic region or third ventricle of the rat caused thirst within a minute or so of injection followed shortly afterwards by increased sodium appetite. Renin from two widely different sources produced identical responses.2. The stimulating effect of renin on intake of water and hypertonic (2.7%) NaCl was continuous and persisted for at least a week after the largest (265 ng) dose of purified renin.3. The stimulating effect was also very large. A single preoptic injection of less than 0.75 pmol (26.5 ng) purified mouse renin caused mean intakes of 250.4 +/- 26.2 ml water and 44.8 +/- 12.5 ml 2.7% NaCl by five naive rats in 24 h. After the largest dose (265 ng) intakes of water and 2.7% NaCl reached about 80% and 20% body weight respectively.4. Weekly injections of renin resulted in progressively larger intakes of NaCl and water in response to the injections.5. Even after repeated injections, carbachol did not stimulate sodium appetite. The stimulating effect on water intake was quickly over and showed no progressive increase with repeated injections. Overnight intake of water was generally depressed after carbachol.6. Preoptic injection of renin caused some increase in sodium excretion but this was small compared with the stimulating effect on sodium appetite.7. Detailed temporal analysis of fluid and sodium balance shows that the increased intakes of water and 2.7% NaCl were not secondary to renin-induced urinary losses. Increased intakes of water and 2.7% NaCl caused by renin resulted in the rats going into and remaining in positive fluid and sodium balance throughout the 24 h experiment.8. Renin-induced sodium appetite and thirst were inhibited by the converting enzyme inhibitors teprotide or captopril, or by the angiotensin antagonist saralasin. Inhibition was longer lasting after captopril. Carbachol-induced thirst was unaffected.9. In conclusion, renin injected into the preoptic region or third ventricle is a potent stimulus to sodium appetite as well as thirst. The effect is mediated by local generation of angiotensin II and it is not secondary to increased urinary loss.

Angiotensin II↗
PubMed1983

Renin dependence of captopril-induced drinking after ureteric ligation in the rat.

In experiments lasting 8 h, low (0.5 mg kg-1) or medium (5 mg kg-1) subcutaneous doses of the angiotensin-converting enzyme inhibitor captopril were mildly dipsogenic in sham-operated rats, much more so in rats subjected to bilateral ureteric ligation and not at all in bilaterally nephrectomized rats. Rats with ligated ureters drank enough water to gain weight during the experiments. All other groups lost weight. The enhanced responsiveness of rats with ligated ureters, despite fluid retention, shows that captopril-induced drinking was not secondary to increased renal fluid loss. Ureteric ligation alone which caused some increase in renin secretion was mildly dipsogenic compared with sham operation. Captopril caused further increases in plasma renin concentration and more drinking suggesting that the captopril response is renin-dependent. The failure of the nephrectomized rat to drink after captopril also shows that the response is renin-dependent. The highest dose (50 mg kg-1) of captopril did not at first stimulate drinking, though water intake increased later. Slowness to drink was not the result of general depression of behaviour since drinking in response to subcutaneous hypertonic NaCl or intracranial angiotensin II was not inhibited by the highest dose. Slowness to drink after the highest dose was attributable to blockade of converting enzyme centrally as well as peripherally. This meant that the increased circulating angiotensin I resulting from peripheral blockade of converting enzyme was only slowly converted to angiotensin II in the brain. When cerebral conversion of angiotensin I was prevented by a single intracranial injection of 25 micrograms captopril, drinking in response to the lower doses of captopril was also inhibited in normal rats and in rats with ligated ureters. The same intracranial dose of captopril also inhibited drinking in response to intracranial injections of renin or angiotensin I, but not angiotensin II. The time course of inhibition of renin-induced drinking was similar to that of inhibition of subcutaneous captopril-induced drinking. In conclusion, subcutaneous captopril causes increased water intake through activation of the renal renin-angiotensin system, an effect that is enhanced when the system has already been partly activated by ureteric ligation. Increased circulating angiotensin I resulting from blockade of peripheral converting enzyme must be converted to angiotensin II in the brain in order to stimulate drinking. Drinking is not the consequence of increased fluid loss.

Angiotensins↗
PubMed1983

Cathepsin D and calcium-activated protease activities in skeletal muscle of normal and protein-deficient pregnant rats.

The role which two proteolytic enzymes (cathepsin D, CD and calcium-activated protease, CAP) might play in the early anabolic and subsequent catabolic phases of skeletal muscle protein metabolism was investigated in rats fed normal and protein-deficient (50 g/kg) diets. Enzyme measurements were performed on crude homogenate and subcellular fractions of mixed thigh muscle. In normal pregnancy there was no evidence that the changes in muscle protein mass which occurred were assisted by changes in the activities of CD or CAP. CAP activity was, however, reduced throughout protein-deficient pregnancy. Electron micrographs of gastrocnemius muscle samples taken on day 21 of pregnancy suggested increased lysosome numbers in the protein-deficient animals. However, the specific activity of CD in the muscle microsomal-mitochondrial fraction from these animals showed decreased specific activity. Thus, neither CD nor CAP play any major role in releasing amino acids from maternal skeletal muscle for placental and fetal use during protein deficiency. Changes in CAP activity in early pregnancy may indirectly help to protect the fetus from protein deficiency by allowing maternal protein mass to accumulate early in pregnancy for catabolism and use at a later stage.

Animals↗
PubMed1982

The effects of lipid fluidity on the rotational diffusion of complex I and complex III in reconstituted NADH-cytochrome c oxidoreductase.

NADH-ubiquinone oxidoreductase (Complex I) can be recombined with ubiquinol-cytochrome c oxidoreductase (Complex III) to reconstitute NADH-cytochrome c oxidoreductase. Two modes of interaction have been found. In one, the Complexes interact stoichiometrically in one to one molar ratios to give a binary Complex I-III unit. In the other, the kinetics of NADH-cytochrome c oxidoreductase are characteristic of 'Q-pool' behaviour seen in intact mitochondria and submitochondrial particles in which the Complexes need not interact directly but can do so via a pool of mobile ubiquinone. Stoichiometric behaviour is found when only boundary layer or annular lipid is present or the lipid is in the gel phase. The lipid is immobile on the ESR time scale and protein rotational diffusion, measured by saturation transfer ESR, is very slow. Q-pool behaviour is found when mobile extra-annular lipid phase is also present. Protein rotational diffusion is rapid and characteristic of a fully disaggregated state. We have also used freeze-fracture electron microscopy of reconstituted NADH-cytochrome c oxidoreductase to monitor protein aggregation and lateral phase separation of lipids and proteins under various conditions. We discuss our findings in relation to models for lateral interactions between respiratory chain enzymes.

Animals↗
PubMed1982

The effects of changes in osmolality and sodium concentration on angiotensin-induced drinking and excretion in the pigeon.

1. The pigeon drank copiously after a short latency in response to intracerebro-ventricular (I.C.V.) infusion of angiotensin II dissolved in isotonic NaCl. There were small, insignificant increases in urinary excertion so that the increased water intake caused the pigeon to go into positive fluid balance. Water was chosen in preference to 0.3 M-NaCl, which was also available to drink in these experiments.2. I.C.V. infusion of angiotensin dissolved in water, or in isotonic or hypertonic solutions of non-eletrolytes, or in KCl or CaCl(2) resulted in about half the water intake produced by angiotensin dissolved in isotonic NaCl.3. I.C.V. infusion of hypertonic NaCl alone caused drinking. I.C.V. infusion of angiotensin dissolved in hypertonic NaCl caused an amount of water to be drunk that was a simple addition of the amounts drunk in response to angiotensin dissolved in isotonic NaCl and to the extra amount of NaCl.4. Drinking in response to I.C.V. infusion of two other dipsogenic peptides, eledoisin and physalaemin, was similarly affected by the composition of the solutions in which they were dissolved.5. The pigeon also drank in response to intravenous (I.V.) infusion of angiotensin II dissolved in isotonic NaCl. Urine flow and sodium excretion increased markedly so that the pigeons just maintained fluid balance.6. In contrast to the reduction in intake when angiotensin was infused I.C.V. dissolved in hypertonic non-electrolytes, I.V. infusions of angiotensin dissolved in hypertonic non-electrolytes caused enhanced drinking, compared with the corresponding infusions of angiotensin dissolved in isotonic NaCl.7. Drinking induced by I.V. infusion of angiotensin was little affected by simultaneous I.C.V. infusion of isotonic or hypertonic sucrose, or water, but it was increased by simultaneous I.C.V. infusion of hypertonic NaCl.8. Drinking responses were partly additive when angiotensin was given by simultaneous I.C.V. and I.V. infusion.9. The increased urine flow and electrolyte excretion in response to I.V. infusion of angiotensin were little affected by simultaneous I.C.V. infusion of angiotensin.10. These experiments suggest that in the pigeon there may be separate sets of receptors in the cerebral ventricles for initiating drinking, one set responding to angiotensin, another to hypertonic NaCl. Outside the blood-brain barrier, and accessible to blood-borne substances, there may also be separate sets of receptors, one set responding to angiotensin, another to increases in effective osmolality of the blood.

Angiotensin II↗