R. D. Wright

Osmoregulatory thirst in sheep is disrupted by ablation of the anterior wall of the optic recess

Ablation of the organum vasculosum of the lamina terminalis (OVLT) and adjacent midline tissue in the anterior wall of the optic recess of the third ventricle resulted in greatly reduced water drinking to intracarotid infusion of hypertonic NaCl in sheep. Daily food and water intake and angiotensin II drinking were not consistently reduced by these lesions. Tissue in or close to the OVLT is probably involved in osmotically induced water-drinking.

THE EFFECT OF ALDOSTERONE, CORTISOL, AND CORTICOSTERONE UPON THE SODIUM AND POTASSIUM CONTENT OF SHEEP'S PAROTID SALIVA*

Sodium depletion in the sheep results in a fall in parotid salivary sodium/potassium concentration ratio (Na/K) from a normal 25 to 40 (Na, 170 to 185 and K, 4 to 6 mEqper L) to as low 0.3 (Na, 40 and K, 133 mEqper L) (1, 2). Earlier work in this laboratory suggested that this reciprocal alteration in the concentration of salivary sodium and potassium was due predominantly to the simultaneous operation of 1) a fall in the salivary secretion rate and 2) an increase in the secretion of electrolyte-active adrenal steroids. If suitable allowance were made for the effects of variation in the parotid salivary secretion rate and the latency of the response, it was proposed that the salivary Na/K ratio could be used as an index of the release of electrolyte-active steroid into the circulation (2-5). Cortisol (6), corticosterone (6), and aldosterone (7-9) have been identified in sheep adrenal venous blood. In order to obtain a basis for evaluating the contribution of each of these components of the adrenal secretion to the fall in parotid salivary Na/K ratio observed during different physiological states, the effects of these steroids upon salivary Na and K were studied in a series of experiments in normal and adrenalectomized sheep.

Control of Adrenal Secretion of Electrolyte-active Steroids—I

PART I Addison (1868) in his original report records the case of a tide waiter whose disease was exacerbated when living on salt provisions which would have been pickled with nitre-that is, potassium nitrate. Loeb, Atchley, Benedict, and Leland (1933) showed that adrenalectomy caused urinary loss of Na+ and a decrease of Na+ and increase of K± in the plasma. The demonstration of Na+-retaining action by deoxycortone acetate (D.C.A.) led to a search for this or a similarly active substance in the adrenals. The discovery of aldosterone, with 25 to 120 times the activity of D.C.A., not only in extracts but in the adrenal venous blood, has led to the acceptance of it as by far the most electrolyte-active steroid (Simpson, Tait, Wettstein, Neher, von Euw, and Reichstein, 1953). It is 500 to 1,000 times more active than cortisol, and 4,000 times more active than corticosterone in causing renal Na+ retention in rats (Swingle, Maxwell, Ben, Baker, LeBrie, and Eisler, 1954; Desaulles, 1958). It is also 100 times more active than these compounds in stimulating K+ excretion. The finding that there is increased urinary excretion of aldosterone in congestive cardiac failure (Deming and Luetscher, 1950; Singer and Wener, 1953) as in other oedematous states (Chart and Shipley, 1953) has raised the question whether increased adrenal cortical activity is a contributory cause of the development of oedema. Such an inference, however, like that proposing a causal relation between intravascular or extracellular volume and aldosterone secretion (Bartter, 1956; Bartter, Biglieri, Pronove, and Delea, 1958) depends on the assumption that the rate of urinary excretion of aldosterone is proportional to the rate of adrenal secretion in all conditions, and is not determined by other factors-for example, altered renal activity or liver metabolism (Wolff, Koczorek, and Buchborn, 1958). The amount of aldosterone excreted in the urine is about 5% of the amount secreted (Ayres, Garrod, Simpson, and Tait, 1957), but studies with labelled aldosterone by Ayres, Barlow, Garrod, Kellie, Tait, Tait, and Walker (1958) suggest that this small proportion may be a valid basis for inference in the instance of simple Na+ deprivation. The understanding of the role of the adrenal cortex in a complex situation like congestive heart failure would probably be simpler if the control of aldosterone

Morphology of the organum vasculosum of the lamina terminalis (OVLT) of the sheep

Examination of the ventricular surface of the organum vasculosum of the lamina terminalis (OVLT) of sheep with the scanning electron microscope revealed an elongated protuberance occupying most of the frontal wall of the third ventricle below the level of the anterior commissure. This protuberance lacked ciliated ependymal cells. Examination of horizontal sections with the transmission electron microscope revealed an apparent lack of regularly apposed ependymal cells, suggesting that ependyma is either greatly modified or absent. The surface was composed of numerous intertwining cell processes with some scattered cells situated on this surface. The body of this structure was composed of many cell processes separated by a network of extracellular channels sometimes extending to the ventricular surface. Towards the base of this protuberance, a plexus of blood vessels was observed. Some of these vessels exhibited fenestrated endothelium. Neuronal processes were also apparent in this region. These unusual anatomical features suggest a specific function for this brain region in sheep.

The onset of effect of ACTH, angiotensin II and raised plasma potassium concentration on the adrenal cortex

Abstract The time course of effect of three direct acting stimuli on aldosterone, cortisol and corticosterone secretion has been examined in the sheep. Angiotensin II and ionic changes are specific for aldosterone and appear to affect the zona glomerulosa alone. ACTH resulted in increased secretion of all three steroids in three of five experiments. The time course of response for the two stimuli specific to aldosterone production was similar to the zona fasciculata response to ACTH. There was no obligatory increase in corticosterone secretion (p > 0.1) as a result of the mobilization of biosynthetic events leading to increase aldosterone secretion. The first detectable changes can occur as early as three minutes and the maximum output for the doses used is reached in 10 – 10 minutes.

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.

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.

THE EFFECT OF ADRENAL CORTICAL STEROIDS ON PAROTID SALIVARY SECRETION

ABSTRACT This paper records detailed observations on the effect of administered corticosteroids, particularly aldosterone, on the Na and K content of the parotid saliva of the sheep. A dose response relation between intravenous administration of physiological amounts of aldosterone and salivary Na/K ratio was demonstrated in Na replete normal and in Na deficient adrenalectomized sheep. It has been shown that infused glucocorticoids at levels similar to those maximally secreted by the sheeps adrenals have little or no effect on the parotid salivary Na/K ratio, but infused aldosterone has equivalent effect of endogenous aldosterone. A striking difference was shown between the sensitivity to aldosterone of the parotid of Na replete and Na deficient sheep. Experiments on intravenous infusion of aldosterone show that the parotid of a 30 kg Na depleted sheep may respond to as little as 1–2 μg/hr. The relevance of these findings to the physiological problems of adaptation of ruminant animals to stringent ecological conditions involving changes in feeding habits is discussed.