J. F. Nelson

ACTH induced sodium appetite in the rat.

Subcutaneous injections of long-acting synthetic ACTH (5 U/day) caused a large increase in the intakes of both 0.5 M NaCl and water in rats. By the fifth day of treatment the rats were turning over an amount of sodium approximating their own total body sodium. The mineral appetite was specific for NaCl. Intakes of KCl, MgCl2 and CaCl2 were unchanged. ACTH was ineffective in adrenalectomized rats suggesting that the appetite was dependent on adrenal hormones.

Dehydration-induced sodium appetite in rats

The effect of 24 hr water deprivation on Na balance was studied in rats. Under baseline conditions, the animals had free access to food and water. During water deprivation, Na excretion was increased, Na intake (i.e., food intake) was decreased and Na deficits of 0.8-1.0 mmol were incurred. During the 24 hr period immediately following the deprivation period when water was returned, Na excretion was decreased and Na balance was restored to baseline or pre-deprivation level. In a second series of experiments, under baseline conditions, the animals had free access to food, water and 0.5 M NaCl. During water deprivation with NaCl solution withheld, Na excretion was not changed relative to baseline but Na deficits of 0.8-1.0 mmol were incurred due to decreased Na intake. During the 24 hr period immediately following deprivation when both water and NaCl solution were returned, intake of the hypertonic NaCl solution was increased and Na balance was restored. In a third series of experiments, under baseline conditions, the animals had free access to food, water, 0.5 M NaCl, 0.5 M KCl, 0.25 M of MgCl2 and 0.25 M CaCl2. During the 24 hr period following water deprivation and also the withholding of the electrolyte solutions, the appetite induced was predominantly for NaCl. The results suggest that the Na appetite observed subsequent to a period of water deprivation may be due to Na deficiency.

Water and salt intake of wild rabbits (Oryctolagus cuniculus (L)) following dipsogenic stimuli.

Wild rabbits trapped in their natural habitat and adapted to laboratory conditions were studied. Food, water and electrolyte (0.5 M‐NaCl, 0.5 M‐KCl, 0.25 M‐MgCl2 and 0.25 M‐CaCl2) consumption, urinary volume and sodium losses were monitored daily following stimuli which were found dipsogenic in other species. Water drinking was observed immediately after the intravenous injection of 1 M‐NaCl (3 ml/kg), and following withdrawal of a mean of 13.9% of calculated blood volume. Daily intake of water decreased during intracerebroventricular (I.C.V.) infusion of 0.3 M‐NaCl in artificial cerebrospinal fluid (c.s.f.), during I.C.V. infusion of 0.9 M‐mannitol c.s.f., both at a rate of 17 microliters/h, following peritoneal dialysis with 5% (w/v) glucose solution, and during food restriction. Water intake was not affected following intravenous administration of acetazolamide (10 mg/kg). Daily intake of 0.5 M‐NaCl solution was increased following peritoneal dialysis with 5% (w/v) glucose solution, which caused hyponatraemia, but not after haemorrhage which caused about the same sodium deficit as peritoneal dialysis, but as an isosmotic loss. Administration of two different angiotensin II analogues, systemically or I.C.V., failed to induce water drinking. However, urinary sodium excretion and intake of 0.5 M‐NaCl were increased during the 5 days of I.C.V. infusion of angiotensin II (10 pmol/h). Infusion for 1 day of angiotensin II (500 pmol/h) led to increased urinary sodium excretion which was followed by increased intake. The intake of other electrolyte solutions was not significantly affected by any of the treatments detailed above. The mechanisms participating in initiation of thirst in wild rabbits are very sensitive to decrease in blood volume, in contrast to other species studied in laboratories. Angiotensin II at the doses and routes administered was not dipsogenic in wild rabbits. The increased intake of 0.5 M‐NaCl solution observed during and after the long‐term intraventricular administration of angiotensin II in the wild rabbit appears predominantly a response to sodium deficit caused by natriuresis. The persistence of appetite after the cessation of infusion is indicative of a residual effect on central mechanisms of salt appetite.

Stress, ACTH, salt intake and high blood pressure.

Epidemiological evidence supports the thesis that high salt intake is involved in the aetiology of hypertension. If sodium intake is not causal, it appears other factors do not cause high blood pressure in unacculturated societies with low sodium intake. In this context, it is potentially important that stress causing ACTH release, as well as other neurohumoral effects, causes increased salt appetite and can impair renal sodium excretion.

THE EFFECT OF PREGNANCY ON MINERALO- AND GLUCO-CORTICOID SECRETION IN THE SHEEP

1. The peripheral blood concentrations of aldosterone, corticosterone and cortisol were measured during pregnancy in conscious, undisturbed sheep.

Circulatory and Humoral Changes in the Reversal of Renovascular Hypertension in Sheep by Unclipping the Renal Artery

The renal arterial clip was removed from 11 sheep with chronic experimental renovascular hypertension (previous unilateral nephrectomy, unilateral renal arterial constriction for 3 to 8 weeks, blood pressure elevated and stable). In five animals cardiac output, blood volume, plasma [Na+], and plasma renin concentration were measured the day before, 1 day after, and 4 days after unclipping. In the other six animals, plasma [Na+], plasma renin concentration, and blood angiotensin concentration were determined before and after unclipping. After unclipping, blood pressure returned to normal levels in 24 to 96 hours; cardiac output and blood volume were essentially unaltered during the period of observation. No natriuresis was seen, nor any change in plasma [Na+], plasma renin concentration, or blood angiotensin concentration, which remained within the appropriate normal ranges throughout. Nephrectomy of five similarly hypertensive animals, and six previously unilaterally nephrectomized normotensive sheep, was performed as a control. Variables similar to those measured before and after unclipping were determined at similar time intervals. The second nephrectomy of hypertensive animals was followed by maintained hypertension; and of normotensive animals by maintained normotension. The role of the kidney in the maintenance and reversal of chronic experimental renovascular hypertension is evaluated in the light of these results.

Ionic, histological and vascular factors in the reaction of the sheep's parotid to high and low mineralocorticoid status

1. The blood capillaries from the alveolar areas of the sheeps parotid gland drain into a sinusoidal portal venous system which is in close relation to the striated intralobular ducts.

REGULATION OF TSH RELEASE

The functional activity of many biological systems is regulated by more than one mechanism. Some of these mechanisms are in the form of servo-controlled systems, and others are specifically designed to alter the activity level of the system. Each mechanism is composed of a number of sequential steps involving different anatomic and functional units. These mechanisms are interrelated either at the final active tissue cell or at one of the intermediate steps of the several mechanisms. The analysis of such controlled systems involves an anatomic and physiological mapping of the several steps of each mechanism and of the interrelationships among them. Such studies are a prerequisite to the more detailed investigations of each step in terms of biochemical mechanisms. We shall describe and criticize the attempts to analyze the mechanisms regulating thyroid stimulating hormone (TSH) release from the pars distalis. No attempt will be made to review the literature, as most of the original references will be found in recent reviews and publication^.^^^^^^^^^^^^^^^^^ The main difficulties in the design and interpretation of experiments dealing with TSH release may be listed. One consists of determining which component of the several mechanisms is the primary site of action of an administered chemical. The close proximity between the hypothalamus and pituitary increases this difficulty. Another is determining the primary effect of ablation or stimulation of one component. A third is that the anatomic limits of certain components are not known: for example, the “thyrotrophin area of the hypothalamus.” It is therefore impossible to be certain that hypothalamic lesions have removed all hypothalamic influence on the pituitary. Similarly, it is not yet known whether interruption of the portal circulation hypophysed by stalk section or pituitary grafts completely eliminates all neural influence on the pituitary. Finally, it should be noted that a mechanism that is studied and found to be operating over a short experimental period may not be identical with the normal long-term regulatory mechanism operating during the day.

The effect of carbonic anhydrase inhibitors on the anionic composition of sheep's parotid saliva. With an appendix on uncatalysed carbon dioxide-water kinetics by P. T. McTigue.

1. The effects of the carbonic anhydrase inhibitors, acetazolamide, ethoxzolamide and benzolamide on the ionic composition of parotid saliva were studied in anaesthetized sheep with access to the parotid blood vessels. 2. The inhibitors were infused directly into the arterial blood supply to the gland to give blood concentrations in the range 10(‐5) to 10(‐2) M. 3. Mean anionic concentrations at basal flow rate before inhibitor infusion were, bicarbonate 98 m‐mole/l., phosphate 15 m‐mole/l. and chloride 26 m‐mole/l. In the presence of inhibitors, bicarbonate concentration fell by 11 m‐mole/ml. and phosphate and chloride concentrations rose. Secreto‐motor nerve stimulation increased bicarbonate concentration by 13 m‐mole/l. before infusion of inhibitors and the concentrations of the other anions fell. The bicarbonate rise was abolished by the inhibitors and the fall in phosphate concentration was balanced by a rise in chloride concentration. 4. These effects show that only a small component of the bicarbonate ion transfer system in the sheep parotid gland is sensitive to these inhibitors. 5. The relationship of these findings to a new enzyme with carbonic anhydrase action isolated from the sheeps parotid gland is discussed.

Changes in sodium appetite in cattle induced by changes in CSF sodium concentration and osmolality.

Alteration of the sodium concentration in the cerebrospinal fluid (CSF) of sheep induces reciprocal changes in sodium appetite. Similar studies have now been performed in cattle. Heifers were prepared with a unilateral parotid fistula and guide tubes were implanted in the skull for the introduction of probes into the lateral ventricles in order to sample CSF and infuse artificial CSF solutions. The cows were Na depleted by loss of saliva for 46 hr and then given free access for 2 hr to 300 mM NaCl/NaHCO3 solution. Artificial CSF infusions at 1.9 ml/hr were begun one hour before Na access. In control experiments, the cows drank 26.4 +/- 1.2 l of Na solution in 2 hr, 1.2 +/- 0.2 l of water in the preceding hour, and 0.3 +/- 0.1 l of water during Na access. Sham or standard isotonic CSF infusions did not alter these values. CSF [Na+] rose from approximately 142 to approximately 148 mmol/l, attributable to the effects of drinking the large volume of hypertonic Na solution. Infusion of 500 mM NaCl CSF increased CSF [Na+] and reduced Na intake and increased water intake. Infusion of 700 mM mannitol: 150 mM NaCl CSF reduced CSF [Na+] and increased both Na and water intake. Infusion of a mixture of these solutions had no effect on CSF [Na+] and increased water intake only. Infusion of 270 mM mannitol CSF reduced CSF [Na+] and slightly reduced Na intake. Standard isotonic CSF containing 0.5 or 2.0 micrograms/ml of angiotensin II increased water intake only.(ABSTRACT TRUNCATED AT 250 WORDS)