Evidence for an influence of CSF sodium concentration upon ACTH-mediated cortisol response to intravenous and intracerebroventricular angiotensin II.

The influence of cerebrospinal fluid (CSF) NaCl concentration upon the cortisol release induced by intracerebroventricular (i.c.v.) and intravenous (i.v.) infusions of angiotensin II (AII) was studied in conscious goats. A first series of experiments involved i.c.v. infusion (20 min; 20 microliters min-1) of simply hypertonic (0.5 M) NaCl, or of AII (2 pmol kg-1 min-1) dissolved in 0.5 M or isotonic (0.15 M) NaCl or in isotonic glucose. The most pronounced rise in plasma cortisol concentration (PC) was elicited by AII in 0.5 M NaCl, but responses of nearly the same size were obtained by merely 0.5 M NaCl and by AII in isotonic NaCl, whereas AII in glucose induced a smaller PC rise. An urge to drink developed during all infusions, except during the AII/glucose infusion. Here, however, thirst became apparent 2-6 min post-infusion. When, in a second series, the hypertonicity of the NaCl was reduced to 0.3 M, and the dose of AII to 0.5 pmol kg-1 min-1, only the infusion of AII in 0.3 M NaCl elicited any appreciable rise in PC. The response was approximately the same size as that earlier obtained as the effect of the larger dose of AII dissolved in isotonic saline. In a third series of experiments, a 30-min i.c.v. infusion of isotonic glucose, preceding and out-lasting a 10-min i.v. infusion of AII (40 pmol kg-1 min-1), was found to extinguish the rise in PC obtained as the effect of a separate i.v. infusion of AII.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone secretion during acute metabolic and respiratory alkalosis in the goat.

Metabolic and respiratory alkalosis were produced in goats with the primary aim of studying possible influence of a reduced blood hydrogen ion concentration on aldosterone secretion. Metabolic alkalosis was induced by 1 h i.v. infusion of hypertonic tris(hydroxy-methyl)aminomethane (THAM) solution. The infusion was associated with a significant reduction in plasma aldosterone concentration (PA). It occurred in the absence of a detectable fall in plasma K or obvious change in plasma renin activity, but simultaneously with a moderate increase in plasma cortisol concentration and a significant reduction of plasma Na concentration. It suggests that changes of the primary aldosterone regulators were not the cause of the fall in PA, but leaves open the possibility that either the decreased blood hydrogen ion concentration as such or THAM-induced blood hypertonicity reduced the aldosterone secretion. The respiratory alkalosis was due to heat polypnoea elicited by 2 h exposure of the goats to 45 degrees C. Here, no obvious change in PA was observed during the alkalotic period, which, however, was associated with a rise in plasma K. Increased K stimulation may therefore have masked a possible inhibitory influence of the alkalosis upon the aldosterone secretion.

Aldosterone secretion during acute respiratory acidosis and NH4Cl-induced metabolic acidosis in the goat.

Acute respiratory acidosis was induced in goats by inhalation of 6% or 8% CO2 in air for 30 min. The lower CO2 concentration caused a significant rise in plasma cortisol (PC), but had no appreciable influence upon plasma aldosterone (PA), and did not affect the arterial blood pressure (aBP). A more pronounced PC response was observed in association with the inhalation of 8% CO2, but also here without concomitant increase in PA. However, the aBP became elevated by about 30% during the CO2 exposure with a simultaneous increase in glomerular filtration rate and a water diuresis, suggesting that the release of arginine vasopressin temporarily became inhibited. It was confirmed that metabolic acidosis induced by duodenal NH4Cl administration is preceded by a transient rise in PA. Dexamethasone-induced feedback inhibition of the ACTH secretion blocked the PA response, which possibly reflects NH4 ion stimulation of the ACTH release. The combined results of the CO2 and NH4Cl experiments seem to justify the conclusion that increases in PA seen in conjunction with acidosis do not reflect a direct hydrogen ion stimulation of the adrenal glomerulosa cells.

Acidosis, hypoxia and stress hormone release in response to one-minute inhalation of 80% CO2 in swine.

The study pertains to a series of investigations on the effects of CO2 inhalation as used for pre-slaughter anaesthesia in swine. Acid/base parameters, blood oxygen tension, plasma Na, K, Ca and stress hormone concentrations were monitored in Yorkshire swine before, during, and for 10 min after the animals were descended for 1 min into 80% CO2 in air. Severe respiratory acidosis (PaCO2 approximately 50 kPa, arterial pH approximately 6.6) and hypoxia (PaO2 approximately 4kPa) had developed after 45 s of the CO2 inhalation. The corresponding changes in venous blood were less drastic (PvCO2 approximately 17 kPa, pH 7.1, PvO2 approximately 4 kPa). Readjustment to PaCO2 approximately II kPa, arterial pH 7.2, and PaO2 approximately 13 kPa had occurred at 1 min post CO2. Four minutes later the respiratory acidosis had become converted into metabolic acidosis subjected to partial respiratory compensation (arterial pH 7.3 in the presence of moderate hypocapnia and hyperoxaemia). The cause of this metabolic acidosis (present also at 10 min post CO2) was apparently hypoxia-induced anaerobic metabolism (= lactic acid production). Apparently due to hydrogen ion transport into the cells in exchange for other cations, hyperkalaemia (K approximately 6.6 mmol l-1), and a 7 mmol l-1 increase in plasma Na had developed at 1.5 min later. The CO2 inhalation did not change the total plasma Ca significantly. The transport of the swine from the stable to the immediate pre-experimental situation induced a 3-fold increase in plasma cortisol concentration (PC, to approximately 130 mmol l-1). No further increase in PC occurred in response to the CO2 inhalation. It indicates that no additional emotional strain was imposed upon the animals during the CO2 exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Endotoxin-induced prostaglandin (PGF2 alpha) biosynthesis, fever and miosis in dexamethasone-treated goats.

Prostaglandin-releasing, adrenocortical, febrile and miotic responses to endotoxin (ET) (E. coli lipopolysaccharide; 0.25 microgram kg-1) were studied in goats with and without prolonged dexamethasone influence. The i.v. injection of ET induced a three-fold peak elevation in plasma 15-ketodihydro-PGF2 alpha at 1.5 h post-injection, that is, between the first and second phase of the temperature elevation. During the latter phase, the plasma concentration of this primary PGF 2 alpha metabolite gradually returned to basal level, which implies that the second phase of ET fever is not PG dependent. The PG response exhibited a similar pattern, but was less pronounced in the dexamethasone-ET experiments, where the duration of maximum temperature elevation and of the miosis became shortened by about 20 min, and the typical biphasic pattern of ET fever was no longer seen. The ET-induced rise in plasma aldosterone concentration was completely blocked by dexamethasone. The corresponding rise in plasma cortisol concentration was prevented for 2 h, but was later only partially inhibited in spite of the repeated dexamethasone treatment.

ACTH-mediated aldosterone hypersecretion during endotoxin-induced fever with apparent influence upon renal sodium excretion.

Febrile, endocrine, and renal responses to i.v. injection of endotoxin (E. coli lipopolysaccharide, 0.25 microgram kg-1) were studied in hyperhydrated goats without, and after dexamethasone pre-treatment, performed with the aim of inhibiting the adenohypophyseal secretion of ACTH. As expected from previous investigations, the administration solely of endotoxin induced biphasic fever, pronounced and long-lasting (less than 4 h) elevation of plasma cortisol (PC), and a prompt inhibition of the water diuresis. Apparently the observation that endotoxin also induced a pronounced biphasic elevation of plasma aldosterone (PA) where the two rising phases coincided with the early, and respectively the second elevation in rectal temperature is original. The endotoxin had no obvious influence upon the renal Na excretion for 3 h post-injection, and did not affect plasma renin activity (PRA). After dexamethasone pre-treatment (0.02 mg kg-1, i.v. 75 min prior to endotoxin) the endotoxin-induced rise in rectal temperature initially was less steep and no biphasic pattern of the fever was observed. The PC and antidiuretic responses became delayed for about 2 h and were then much attenuated. Endotoxin-induced rise in PA was no longer observed, and a conspicuous natriuresis developed within 90 min post-endotoxin. It is concluded that endotoxin at the dose used causes liberation of ACTH to such an extent that adrenocortical hypersecretion not only of glucocorticoids, but also of aldosterone occurs. The observed differences in Na excretion suggest that this aldosterone hypersecretion may be of pathophysiological importance as a protection against inappropriate renal waste of Na during the early phase of endotoxin-induced fever.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic and centrally mediated angiotensin II effects in the horse.

The primary aim of the study was to evaluate the potential value of intravenous (i.v.) infusion of angiotensin II (AII) for phonocardiographic differential diagnosis of equine valvular insufficiency. Ten-minute AII infusions at 4.5-33 pmol kg-1 min-1 induced clear-cut dose-dependent rises in systemic arterial blood pressure (aBP), whereas the pulmonary aBP remained largely unaffected. It implies that i.v. infusion of AII at about 10 pmol kg-1 min-1 could be a valuable tool for the acoustic differentiation between mitral and tricuspid valvular dysfunction in the horse. The infusion at, and above 9 pmol kg-1 min-1 caused increased heart rate. This chronotrophic effect was not strictly dose-dependent and exhibited significant tachyphylaxis. Angiotensin II administration at, or above 9 pmol kg-1 min-1 was needed to induce an urge to drink, suggesting that angiotensin-induced thirst does not appear in the euhydrated horse until the octapeptide reaches supraphysiological blood concentration. Determinations of plasma aldosterone concentration (PA) revealed comparatively high morning control values (269 +/- 46 pmol-1). Three consecutive AII infusions with 10-min intervals and at increasing dosages caused a cumulative, almost fourfold elevation of PA. The PA pattern indicated that AII-induced hypersecretion of aldosterone continued for several minutes after the end of the infusions, but also showed that the metabolic clearance of the hormone took precedency of the secretion within 20 min post-infusion. In two of the horses a fall in PA occurred during a fourth, final infusion, indicating that in these instances the previous AII administration had impoverished the store of aldosterone available for release from the adrenal cortex.

Ammonium chloride induced acidosis and aldosterone secretion in the goat.

Responses to 30-min intraduodenal infusion of NH4Cl (total amount 75 mmol) were studied in conscious goats. The infusion caused an immediate, transient rise in plasma aldosterone concentration (PA) from a mean of 78 to 221 pmo l-1. As expected, the NH4Cl administration also induced metabolic acidosis, initially subjected to partial respiratory compensation. The acidosis did not become fully developed until 1 h after cessation of the infusion, when PA had almost returned to its initial level. Renal compensation of the acidosis was shown by acidification of the urine and reduced Na excretion being most pronounced 1-2 h post-infusion. During the infusion blood haemoglobin concentration and the haematocrit increased by 25 and 13%, respectively, without simultaneous increase in plasma protein concentration and with persisting ear vasodilatation, indicating a mobilization of stored erythrocytes in the absence of a general increase in sympathetic tone. The results suggest that the reduction of blood pH is not the cause of the increase in PA occurring in association with NH4Cl-induced metabolic acidosis, but leave open the possibility that this increase may be due to some centrally mediated or direct adrenal influence of NH+4. As regards the apparent NH4Cl-induced mobilization of stored erythrocytes, it is suggested that such a response may play a role in the defence against acidosis by increasing the buffering capacity of the circulating blood.

Influence of heat exposure on acid/base and fluid balance in hyperhydrated goats.

Hyperhydrated goats were exposed to an environmental temperature of 45 degrees C (relative humidity 70%) for 120 min. After 90 min, rectal temperature and respiratory frequency reached plateau levels of 40.5 degrees C and 280 respirations min-1, respectively. Measurements of arterial and venous blood acid-base parameters revealed that respiratory alkalosis had started to develop after 60 min, and had become obvious at the end of the heat exposure period. Renal compensation (evidenced by gradual increases in urinary pH and renal Na excretion) developed in parallel with the respiratory alkalosis. The heat exposure elicited a moderate, temporary inhibition of the water diuresis, but no obvious increase in the renal excretion of arginine vasopressin (antidiuretic hormone, ADH). Preliminary determinations of plasma aldosterone did not show any change during the actual heat exposure period, but a 50% temporary decrease in plasma aldosterone 30 min thereafter. The study confirms the susceptibility of goats to develop respiratory alkalosis during thermoregulatory panting, and shows that this is not to any appreciable extent diminished during hyperhydration. It can further be concluded that a heat-induced rise in body temperature to 40.5 degrees C is no powerful stimulus for vasopressin release in the hyperhydrated goat. The determinations of plasma aldosterone suggest that reduced liberation of the hormone does not contribute to the immediate renal compensation of respiratory alkalosis, but that respiratory alkalosis reaching a certain intensity inhibits aldosterone secretion.

Effects of hay-feeding on acid/base balance, renal sodium excretion, aldosterone and vasopressin secretion in the goat.

Effects of 30 min intense hay-feeding on acid/base and sodium homeostasis were studied in semi-starved goats during hyper- and euhydration. Parallel analyses of carotid and jugular blood samples revealed that feeding induced metabolic acidosis, which to some extent was subjected to respiratory compensation. The acidosis was accompanied by renal sodium retention and urinary acidification persisting for 2-3 h. The sodium retention was succeeded by an increase in renal Na excretion above the initial level. This natriuresis was most accentuated during hyperhydration. Blood samples taken for hormone assays during euhydration revealed a 15% increase in haematocrit and a significant rise in plasma aldosterone at termination of feeding. Inhibition of the water diuresis in hyperhydrated animals, and moderate increases in renal arginine vasopressin (AVP) excretion and plasma AVP were inconsistent effects of feeding. It is concluded, that simply jugular vein blood provides reliable information on the acid/base status of goats, but that the feeding schedule has to be considered in all experiments where small ruminants are used to investigate the integrated control of acid/base and sodium homeostasis.