The effect of sodium balance on sweat sodium secretion and plasma aldosterone concentration

The effect of manipulating sodium intake upon sweat sodium secretion was investigated during heat acclimation. Twenty-five male subjects were confined to an environmental chamber at a temperature of 25°C for 3 days, and then acclimated to heat by a further 5 days at 40°C. The subjects' daily sodium intake was controlled throughout as follows: high (HNa), 348.4 (0.8) mmol · day⁻¹, n = 7; moderate (MNa), 174.1 (0.6) mmol · day⁻¹, n = 9; or low (LNa), 66.3 mmol · day⁻¹, n = 9. Sodium losses were estimated from urinary, faecal and sweat collections using a whole-body washdown method. Plasma aldosterone concentration was also measured from venous blood sampled each morning. Measurements of body temperature and heart rate during the heat exposure phase indicated a degree of heat acclimation. During this heat phase there was a reduction (P < 0.01) in sweat sodium secretion for all three conditions which was greatest for the LNa condition, although this finding was not significant (P < 0.1). In the LNa condition, plasma aldosterone concentration increased (P < 0.05) prior to heat exposure, and the secretion of aldosterone was potentiated (P < 0.01) during the heat exposure in comparison with the MNa condition. In contrast, the HNa diet produced a fall (P < 0.05) in plasma aldosterone concentration prior to heat exposure and an attenuation of aldosterone secretion thereafter. These findings are inconsistent with the hypothesis that retention of sweat sodium is dependent upon a net body sodium deficit, but demonstrate that aldosterone secretion is potentiated under such conditions. Accepted: 22 May 1988     

Dopaminergic control of aldosterone secretion in hypertensive patients chronically treated with an angiotensin converting enzyme inhibitor

To investigate whether dopamine plays a role in the regulation of aldosterone secretion during long-term blockade of the renin-angiotensin system, we studied the effect of metoclopramide, a competitive antagonist of dopamine, in 6 patients with essential hypertension chronically treated with the angiotensin converting enzyme inhibitor enalapril. All but one of these patients received a diuretic in addition to enalapril. Six hours after the daily morning dose of enalapril (10-40 mg p.o.) a 10 mg bolus dose of metoclopramide was injected intravenously. In one patient a hypotensive episode developed following metoclopramide administration. In the 5 other patients plasma aldosterone significantly rose within 30 min after metoclopramide from 51 +/- 8.7 to 128.2 +/- 29.2 pg/ml. This metoclopramide-induced release of aldosterone occurred in the absence of concomitant changes in circulating angiotensin 11, potassium and ACTH levels. Metoclopramide given during chronic blockade of the renin-angiotensin system caused anxiety and agitation in 2 patients. The increase in plasma aldosterone following competitive dopamine blockade in the face of chronic angiotensin converting enzyme inhibition, unchanged plasma potassium and ACTH levels strongly suggests that in hypertensive patients, dopamine exerts a direct inhibitory effect on aldosterone secretion.     

Inhibitors of aldosterone secretion

Aldosterone secretion may be inhibited by potassium depletion, inhibitors of the renin-angiotensin system, dopamine and atrial natriuretic factor. The latter appears to be an important physiological regulator of aldosterone secretion. ANF inhibits basal, ACTH, Angiotensin II and potassium-stimulated aldosterone production in vitro by a direct action on the adrenal gland. In vivo data also support a direct inhibitions of aldosterone. The stimulation of aldosterone secretion by infusions of Angiotensin II and potassium is inhibited by simultaneous infusions of ANF. Infusions of ANF lower the basal aldosterone secretion in man. The mechanism by which ANF inhibits aldosterone is not known. No unifying first step has been identified to explain ANF's ability to inhibit all stimuli. In vivo, part of the lowering of aldosterone levels may be due to inhibition of renin secretion. This effect of ANF upon renin is inconsistent and appears to depend upon the experimental conditions.     

Dopaminergic modulation of arousal in Drosophila

BACKGROUND: Arousal levels in the brain set thresholds for behavior, from simple to complex. The mechanistic underpinnings of the various phenomena comprising arousal, however, are still poorly understood. Drosophila behaviors have been studied that span different levels of arousal, from sleep to visual perception to psychostimulant responses. RESULTS: We have investigated neurobiological mechanisms of arousal in the Drosophila brain by a combined behavioral, genetic, pharmacological, and electrophysiological approach. Administration of methamphetamine (METH) suppresses sleep and promotes active wakefulness, whereas an inhibitor of dopamine synthesis promotes sleep. METH affects courtship behavior by increasing sexual arousal while decreasing successful sexual performance. Electrophysiological recordings from the medial protocerebrum of wild-type flies showed that METH ingestion has rapid and detrimental effects on a brain response associated with perception of visual stimuli. Recordings in genetically manipulated animals show that dopaminergic transmission is required for these responses and that visual-processing deficits caused by attenuated dopaminergic transmission can be rescued by METH. CONCLUSIONS: We show that changes in dopamine levels differentially affect arousal for behaviors of varying complexity. Complex behaviors, such as visual perception, degenerate when dopamine levels are either too high or too low, in accordance with the inverted-U hypothesis of dopamine action in the mammalian brain. Simpler behaviors, such as sleep and locomotion, show graded responses that follow changes in dopamine level.     

Age and the effect of adrenocorticotropic hormone on aldosterone secretion in rats

Age-related changes in functional activity of the glomerular zone were studied in the adrenal cortex of Wistar rats. It was shown that secretion of the basic mineralocorticoid hormone aldosterone was decreased with age. The glomerular zone of old rats showed the reduced sensitivity to the stimulant action of corticotropin, marked by the pronounced reaction to less doses of the hormone administered. At the same time the reactivity and the range of shifts in the course of ACTH dosage build-up decrease with aging.     

Metoclopramide fails to stimulate aldosterone secretion and inhibits serotonin-mediated aldosterone secretion in the rat

The acute and chronic effects of metoclopramide on aldosterone secretion in the rat model were examined. Metoclopramide 50 micrograms iv in dexamethasone-treated rats did not increase plasma aldosterone concentration. Chronic infusion of metoclopramide (72 micrograms/hr) over 5 days also did not show any increase in the plasma or urinary aldosterone concentration when compared with control rats. Metoclopramide in vitro showed no effect on aldosterone secretion from rat adrenal capsular cells but it inhibited serotonin-mediated aldosterone secretion from the same cells significantly.     

Dopaminergic control of aldosterone: modulation of the response of rat adrenal zona glomerulosa cells to alpha-Msh by pretreatment with bromocriptine or metoclopramide

Bromocriptine treatment in rats (3 mg/kg per day, 7 days) significantly reduced alpha-msh and aldosterone plasma levels 2 hrs after the final treatment in animals on low, normal and high sodium diets. Alpha-MSH dose response curves for corticosterone and 18-hydroxydeoxycorticosterone (18-OH-DOC) in subsequently incubated glomerulosa cells gave stimulation at lower concentrations of alpha-MSH (10(-10) moles per litre) than in cells from untreated animals (10(-9) moles per 1). Curves for aldosterone (ald) and 18-hydroxycorticosterone (18-OH-B) were also affected in cells from animals on a low sodium diet. Fasciculata-reticularis cell responses to ACTH were unaffected. Metoclopramide (4 mg/kg per day, 7 days) elevated plasma alpha-MSH, although ald was unaffected, but inhibited the glomerulosa cell response to alpha-MSH in vitro. Acute dopaminergic responses in plasma ald may be mediated through alpha-MSH in rats, but chronically alpha-MSH may down- regulate glomerulosa cell alpha-MSH receptors. It is unlikely that alpha-MSH mediates the adrenocortical response to sodium depletion.     

Intracellular mediators of potassium-induced aldosterone secretion

We have investigated the intracellular messengers of potassium in eliciting aldosterone secretion in calf adrenal glomerulosa cells since there were unresolved issues relating to the role of phosphoinositides, cAMP and protein kinases. We observed no evidence of hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) in 3H-inositol labeled alf adrenal cells or increase of cAMP in response to potassium. Addition of calcium channel blocker, nitrendipine after stimulating adrenal glomerulosa cells with potassium, markedly inhibited aldosterone secretion. A calmodulin inhibitor (W-7) produced greater reduction of aldosterone secretion than an inhibitor of protein kinase C (H-7). These results suggest that a rise in cytosolic free calcium concentration through voltage-dependent calcium channel and calmodulin are the critical determinants of aldosterone secretion stimulated by potassium.     

Dopaminergic modulation of sucrose acceptance behavior in Drosophila

For an animal to survive in a constantly changing environment, its behavior must be shaped by the complex milieu of sensory stimuli it detects, its previous experience, and its internal state. Although taste behaviors in the fly are relatively simple, with sugars eliciting acceptance behavior and bitter compounds avoidance, these behaviors are also plastic and are modified by intrinsic and extrinsic cues, such as hunger and sensory stimuli. Here, we show that dopamine modulates a simple taste behavior, proboscis extension to sucrose. Conditional silencing of dopaminergic neurons reduces proboscis extension probability, and increased activation of dopaminergic neurons increases extension to sucrose, but not to bitter compounds or water. One dopaminergic neuron with extensive branching in the primary taste relay, the subesophageal ganglion, triggers proboscis extension, and its activity is altered by satiety state. These studies demonstrate the marked specificity of dopamine signaling and provide a foundation to examine neural mechanisms of feeding modulation in the fly.     

Lack of prostaglandin effect on sodium balance and hyperreninemia in adrenalectomized rats

Glucocorticoids are known inhibitors of prostaglandin production. Prostaglandin E2 (PGE2) and prostacyclin (PGI2) are promoters of natriuresis and renin release. Excessive prostaglandin production, therefore, might contribute to the altered sodium balance and renin release observed in primary adrenal insufficiency. To test this hypothesis, sodium balance and prostaglandin production were measured in adrenalectomized rats and in animals receiving prostaglandin inhibitors or replacement dexamethasone. Compared to sham-operated controls, adrenalectomized rats had decreased two-day sodium balance and elevated plasma renin concentration (PRC), renal PGE2 production, and renal 6-ketoprostaglandin F1α (6kPGF1α, the nonezymatic metabolite of PGI2); however, no appreciable change in aortic 6kPGF1α production was observed. Dexamethasone given to adrenalectomized rats normalized PRC but had no effect on sodium balance or prostaglandin production. Likewise, prostaglandin inhibitors did not alter the sodium balance or decrease the PRC post adrenalectomy.These data confirm renal prostaglandin production is increased in adrenalectomized rats, but suggest that the elevation is not due directly to glucocorticoid deficiency. Further, PRC levels in adrenal insufficiency do not appear to be prostaglandin mediated. In conclusion, excessive renal prostaglandin production does not contribute to altered sodium balance or increased PRC in adrenalectomized rats.