Effect of bromocriptine on the control of plasma aldosterone diurnal variation in normal supine man.

In order to investigate the role of prolactin in the control of the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), cortisol (PC), aldosterone and prolactin (PRL) levels were determined in samples at 4-hour intervals from 5 normal supine men over a period of 24 h under basal conditions and subsequently over a period of 24 h during suppression of prolactin release by bromocriptine (CB-154). After suppression of prolactin, statistically signific1nt circadian rhythms in PC and PA have been detected with a moderate decrease of PA concentration, while the PC level remained unalterated. PRA rhythmicity persisted with a significant shift of acrophase and remarkable reduction of plasma levels. Moreover, during CB administration a significant correlation was obtained between PA and PC, while no correlation was detected between PA and PRA. These data are consistent with the following concepts: (a) the prolactin does not play a significant role in the regulation of circadian rhythm and concentration of plasma aldosterone in normal supine men, and (b) bromocriptine induces a remarkable reduction of PRA and a variable decrease in plasma aldosterone, but it does not influence the secretion of cortisol in normal subjects.     

Diurnal rhythm in the counts and types of milk somatic cells,neutrophil phagocytosis and plasma cortisol levels in Karan Fries cows during different seasons and parity

Chances of mammary infections are comparatively higher in high producing cows during harsh environmental conditions and are usually characterised by changes occurring in various somatic cells secreted in the milk and their activities. The present study was conducted to record diurnal rhythmicity in milk somatic cell counts (SCC), neutrophil: macrophage (N: M) ratio, phagocytic activity (PA) of milk neutrophils and plasma cortisol concentrations during different seasons and parity in high producing Karan Fries cows. Values of milk SCC, N: M ratio and plasma cortisol levels were lowest during thermoneutral (TN), intermediate in winter and highest during the summer season. Diurnal rhythm in the milk SCC and N: M ratio was noticed in the summer while plasma cortisol exhibited diurnal rhythm in both winter and summer seasons. Milk SCC, N: M ratio and plasma cortisol increased in multiparous cows, but diurnal variation was noticed only in the N: M ratio and plasma cortisol in cows having more than four parity. Phagocytic activity of milk neutrophils was highest during TN, intermediate in winter and lowest during the summer season. Phagocytic activity was higher and similar in cows up to fourth parity but decreased in subsequent lactation cycles. Diurnal rhythm in the PA was noticed in winter and summer seasons and in cows having more than four parity where morning samples showed higher phagocytosis as compared to the evening samples. These results can be used for immunomodulatory interventions and therapeutic approaches in treating mastitis of crossbred cows reared under tropical conditions.     

Circadian rhythms of plasma renin, aldosterone and cortisol on habitual and low dietary sodium intake

To examine the effects of reducing sodium intake upon the renin-angiotensin-aldosterone system (RAAS), 5 healthy men and 5 healthy women, 17-37 years old, living under standardized conditions, were sampled around the clock, once on habitual and once on restricted sodium intake. Plasma renin activity (PRA), aldosterone (PA) and cortisol (PC) were determined by radioimmunoassay. All three variables were found to exhibit a statistically significant circadian rhythm, both on habitual and restricted salt intake. After salt restriction, an increase in midline-estimating statistic of rhythm (mesor) of PRA and PA, but not of PC, was observed. The acrophase (an estimate of the time of high values) for PC lagged behind that for PRA and PA. This difference in acrophase was of specially high statistical significance when subjects were on a sodium-restricted diet. These results demonstrate the importance of inferential statistical so-called rhythmometric methods: parameters such as the acrophase can also be used for the assessment of novel effects and for a quantification in time. The derivation of confidence intervals for each rhythm parameter allows one to verify that a given variable exhibits values bracketing an average not only between a higher and a lower, but also between an earlier and a later limit. Changes that may involve only the acrophase, such as a lead or lag, as here noted, are then detected and are of factual as well as methodological interest.     

A diurnal plasma vasopressin rhythm in rats

The purpose of this paper was to determine whether there is a diurnal plasma arginine vasopressin (AVP) rhythm in rats. Using an AVP radioimmunoassay, plasma AVP levels were determined at frequent intervals throughout a 24-hour period in adult male rats. Our data revealed a diurnal rhythm in plasma AVP levels, with mid-afternoon and early evening levels significantly greater than those in the morning and late evening.     

Regulations of plasma aldosterone in young hyperkalemic patients with stable chronic renal failure.

In a group of four young patients with stable chronic renal failure and hyperkalemia sodium restriction induced a remarkable increase in plasma renin activity (PRA) and plasma aldosterone (PA), a decrease in the elevated serum potassium (SK) and a rise in potassium excretion. During high sodium intake the levels of PRA and PA were lower than those found in the healthy control group suggesting that enhanced suppressibility of the renin-angiotensin-aldosterone system (RAAS) was the main cause of hyperkalemia. During sodium restriction despite a marked increase in PRA and PA levels poor correlations were found between these variables indicating disorganisation within the RAAS and probably a diminished role for renin-angiotensin in the regulation of aldosterone production in three hyperkalemic patients with chronic glomerulonephritis. On the other hand, in the same patients significant correlations were found between fluctuations of SK and PA on constant normal and low sodium diets supporting the concept of an (at least) equal role of potassium and RAAS in the acute regulation of PA. A prominent role for SK was found in an unusual hyperkalemic patient with interstitial nephritis when PRA was suppressed and the elevated SK showed a definite postural rise inducing dramatic increases in PA in the upright posture. Reversion of the postural SK rise masked again the governing role of SK.     

Plasma renin activity and aldosterone concentration in children.

Using semi-micro methods, plasma renin activity (PRA) and plasma aldosterone concentration (PA) were measured concurrently in 79 healthy children aged 1 month to 15 years to establish a reference range. PRA and PA varied inversely with age. Eleven children with renal hypertension had higher PRA and PA than age-matched controls. In contrast, PRA was much greater in 38 saline-depleted children. PA was not uniformly increased in this group and was within the normal range in children with adrenal diseases compared with the high values seen in other salt-wasting states. The findings emphasise the need to relate data from patients to age-matched control values before attempting interpretation and suggest that sodium depletion is a more potent stimulator of renin-aldosterone release than renovascular disease or renal scarring in children. Plasma renin-aldosterone profiles were also valuable in discriminating between renal and adrenal causes of salt loss in childhood.     

Glucocorticoid effects on the diurnal rhythm of circulating leptin levels

It is known that circulating leptin shows diurnal variation with a nocturnal rise; however, the mechanisms generating this rhythm have not been fully elucidated. Glucocorticoids are a potent stimulator of leptin secretion, and there is a reciprocal relationship between circulating leptin and glucocorticoid levels. We hypothesized that glucocorticoids could modulate the diurnal rhythm of circulating leptin. We therefore explored the diurnal variation of leptin under situations in which subjects showed no or some shift of glucocorticoid diurnal rhythm, such as prednisolone-administered humans, and adrenalectomized and corticosterone-replaced (ADX+B) rats. The peak level of plasma cortisol immunoreactivity was shifted from early morning to noon by prednisolone administration. The nocturnal increment of plasma leptin in prednisolone-administered patients (71.2 +/- 14.2% from 08:00 h value) was significantly greater than that in normal volunteers (12.2 +/- 7.5% from 08:00 h value), but the timing of nadir and the peak of plasma leptin was not shifted. In normal rats, the plasma concentration of leptin showed the diurnal rhythm with the bottom at 16:00 h and the top between midnight and early morning. The amplitude of leptin diurnal rhythm was significantly reduced in ADX+B rats (08:00 h: 3.0 +/- 0.2, 16:00 h: 2.7 +/- 0.2, 00:00 h; 3.7 +/- 0.2 ng/ml) compared with sham operated rats (08:00 h: 3.0 +/- 0.2, 16:00 h 2.2 +/- 0.2, 00:00 h: 4.7 +/- 0.4 ng/ml); but ADX+B rats still retained similar timing of nadir and the peak of plasma leptin as observed in sham rats. These results indicate that glucocorticoids enhance the amplitude of leptin diurnal rhythm, and are consistent with previous findings showing that glucocorticoids increase leptin secretion. Glucocorticoids appear to play modulatory, but not essential roles in generating leptin diurnal rhythm.     

Responsiveness of plasma aldosterone to angiotensin II in patients with diabetes mellitus

Aldosterone responsiveness to angiotensin II (A II) was evaluated in 65 diabetic patients with and without various diabetic complications versus 38 age-matched non-diabetic subjects. Plasma aldosterone (PA), together with plasma renin activity (PRA), was low and responded poorly to furosemide (80 mg, orally) plus upright posture (4 hours) stimulation in diabetic patients. When the PA response to stimulation relative to PRA response was estimated from the ratio of PA increase to PRA increase after stimulation (delta PA/delta PRA), the 38 non-diabetic subjects had ratios more than 3.0. Of the 65 diabetic patients, 48 had normal delta PA/delta PRA ratios (more than 3.0) and 17 had low delta PA/delta PRA ratios (less than 2.9). Graded A II infusions (1, 2, and 4 ng/kg/min each for 30 min) were performed under a low sodium intake (sodium, 120 mEq/day) in 25 of the 65 diabetic patients, whose delta PA/delta PRA ratios were normal in 15 and low in 10, and in 16 non-diabetic subjects. The PA responses to the graded A II infusions in the normal delta PA/delta PRA diabetic patients were similar to those in the non-diabetic subjects. However, the PA responses to the graded A II infusions in the low delta PA/delta PRA diabetic patients were significantly lower. It is concluded that, although the majority of diabetic patients have normal aldosterone responsiveness to A II, some diabetic patients have blunted aldosterone responsiveness to A II probably attributable to the abnormality of the adrenal cortex in addition to the impaired renin secretion.     

Circadian variations of plasma renin activity (PRA), aldosterone and electrolyte concentrations in plasma in pregnant and non-pregnant goats

The aim of this study was to estimate and analyse circadian variations of the renin-angiotensin-aldosterone system (RAA) activity in blood of goats and the influence of late pregnancy on the circadian variations of RAA system. The study was carried out on a group of 17 non-pregnant and 9 pregnant goats. The animals were kept in uniform environmental conditions, (9 h light/15 h darkness). Blood samples were collected seven times over a period of 24 h, every 4 h. Plasma renin activity (PRA), plasma aldosterone (PA), sodium, potassium and chloride concentrations were determined. PRA and PA of both groups changed during 24 h, with the highest values in the dark phase and with higher RAA system activity (especially during the night) in the pregnant goats. In the non-pregnant goats, no circadian changes in PRA and PA were observed. The circadian changes in PRA and PA found in pregnant goats had acrophases at 06:27 h and 01:13 h, respectively. Plasma electrolyte concentrations in both groups of goats also changed during 24 h. These results suggest that circadian changes of potassium concentration in plasma of goats during late pregnancy may be one of the main factors affecting the RAA system.     

Immunoradiometric assay of active renin versus determination of plasma renin activity in the clinical investigation of hypertension, congestive heart failure, and liver cirrhosis

We compared the determination of plasma renin activity (PRA) and the direct immunoradiometric measurement of active renin (AR) as ways of assessing the activity of the renin-angiotensin system in normal volunteers and in patients with hypertension, heart failure, or liver failure. The levels of plasma renin substrate, angiotensinogen, and the ratio of PRA to AR concentration did not differ in the normal volunteers and the patients with essential or renovascular hypertension. However, compared to the volunteers, patients with severe heart or liver failure had markedly reduced plasma renin substrate levels, which led to a considerable underestimation of AR concentration when it was measured by PRA.     

Dopamine control of aldosterone secretion in end-stage renal failure

The role of the tonic inhibitory effect of dopamine on aldosterone secretion has been investigated in 10 patients with chronic renal failure (CRF) on hemodialysis, in 8 normotensive renal transplant recipients (Tx) with normal renal function and in 8 normotensive volunteers (NV). The following tests were performed: the response of plasma aldosterone (PA) to metoclopramide administration; the response of plasma prolactin (PRL) to TRH administration, and the changes induced by Lisuride (a dopaminergic agonist, on the values of PA and PRL). The basal values of PA and PRL were higher in CRF than in NV and Tx. The inverse was true for plasma renin activity (PRA) values. The response of PA and PRL to metoclopramide showed blunted increases in CRF when compared to NV, in the absence of changes of PRA, cortisol and potassium. After TRH administration, PRL increase in CRF was also inferior. Lisuride induced a decrease of both PA and PRL both in CRF and NV. In Tx, basal values of PA and PRL were similar to NV. Nevertheless, the response to metoclopramide and TRH were partially blunted when compared to that of NV. These results point to the existence of a deranged dopaminergic regulation of aldosterone secretion in end-stage renal failure patients. The alterations are partially corrected by a well-functioning kidney graft.     

Influence of physical training on blood pressure, plasma renin, angiotensin and catecholamines in patients with ischaemic heart disease

Eighteen patients with ischaemic heart disease were trained for 3 months, three times a week. The effectiveness of the training programme was demonstrated by increases of 27% in peak oxygen uptake and 29% in exercise duration, and by a decrease in resting and submaximal heart rates. Blood pressure, however, was not significantly affected during the training period. At rest and at submaximal exercise plasma renin activity (PRA) was lower after training. Plasma angiotensin I concentration (PA I) and angiotensin II concentration (PA II) were not significantly affected. Plasma aldosterone concentration (PAC), only measured at rest, was not significantly changed after the training period, while plasma norepinephrine (PNE) and epinephrine (PE) concentrations were significantly decreased, but only at high levels of exercise. A reduced sympathetic tone after training, suggested by the lower heart rates and the tendency to a decrease in PNE, is a likely explanation for the decrease in PRA. However, despite this decrease, PA I, PA II, and PAC were not significantly changed after training; the reason for this disrepancy is unknown.     

Diurnal rhythm of plasma immunoreactive corticotropin-releasing factor in normal subjects

Plasma corticotropin-releasing factor (CRF), corticotropin (ACTH) and cortisol levels were simultaneously determined by radioimmunoassays at 0600 h, 1200 h, 1800 h and 2200 h in six normal subjects, in order to examine whether the diurnal rhythm in plasma CRF exists and how it correlates to the diurnal rhythm in plasma ACTH and cortisol concentration. The highest CRF level was observed at 0600 h (7.0 +/- 1.2 pg/ml) and significantly lower levels (p less than 0.01) at 1800 h (1.7 +/- 0.2 pg/ml) and 2200 h (1.9 +/- 0.4 pg/ml). A clear diurnal rhythm was demonstrated in plasma ACTH and cortisol levels, with the highest values at 0600 h (44.6 +/- 8.1 pg/ml and 15.9 +/- 2.0 micrograms/dl, respectively) and the lowest at 2200 h (12.3 +/- 2.8 pg/ml and 4.6 +/- 1.0 micrograms/ml, respectively). These results suggest that the diurnal rhythm in ACTH and cortisol is under the regulation, at least in part, of the diurnal rhythm in CRF secretion.     

Effects of angiotensin I-converting enzyme inhibitor, SQ 14225, in nomal men.

Effects of an orally active angiotensin I-converting enzyme inhibitor, SQ 14225, on the actions of angiotensin I (AI) infused intravenously for 120 to 390 min were studied in 5 normal men. When 20 ng/kg/min of AI infusion was started immediately after a single oral administration of 100 mg of SQ 14225, a significant rise in blood pressure (BP) was observed for the first 15 min, but BP began to fall from 17 min and returned to the pretreatment level at 45 min. This BP level continued at least to 120 min and in one subject to 180 min. In this subject BP began to rise again from 185 min and reached the level of 15 min at 390 min. Plasma AI level increased gradually from 45 min. At 15 min plasma renin activity (PRA) decreased and plasma aldosterone (PA) increased, but then PRA began to increase and PA began to decrease. At 120 min the values of PRA and PA were similar to the pretreatment values. In one subject plasma AI and PRA began to decrease and PA began to increase after 120 or 180 min. On the other hand, in the 5 men sole AI infusion caused a continued BP rise, PRA decrease and PA increase, and sole SQ 14225 administration caused increases in plasma AI and PRA and a decrease in PA but no BP change. From these results it was concluded that complete blockade and partial inhibition of AI conversion by 100 mg of oral SQ 14225 lasted for about 2.5 and 6.5 hr, respectively and that BP rise, PRA suppression and aldosterone stimulation after AI infusion were entirely due to the actions of angiotensin II converted from AI.     

Influence of pregnancy and lactation on diurnal and seasonal changes in lactic acid and pyruvic acid levels and in values of pH, pCO2 and pO2 in the mare blood.

1. The diurnal changes in the levels of lactic (LA) and pyruvic (PA) acids and in values of pH, pO2 and pCO2 were studied in the blood of barren and later on in pregnant and lactating mares, throughout three subsequent years. 2. Blood samples were taken every 4 hr, for one day, each month, throughout 3 years. 3. The mares were kept and fed in the same conditions, lighting was natural. 4. In barren mares, diurnal rhythm in LA, PA, pO2 and pCO2 was found. 5. The pregnancy as well as lactation masked diurnal rhythms in parameters studied, except the LA level during lactation but then the acrophase was shifted by 3-4 hr. 6. Seasonal cyclicity was found in the values of LA, PA and pCO2 in barren mares. The pregnancy abolished cyclicity in LA level and modified the behaviour of PA and pCO2 values causing a shift of acrophases and lowering the amplitudes of the indices. 7. In the pO2 tensions no seasonal cycles were observed. 8. In the values of pH neither diurnal rhythms nor seasonal cycles throughout study years were observed.     

Episodic secretion of opioid activity in human plasma and monkey CSF: Evidence for a diurnal rhythm

Using a radioreceptor assay, opioiod activity has been determined in human plasma and monkey CSF at two-hour intervals across a 24-hour period. In both human plasma and monkey CSF, opioid activity showed an episodic secretion and a significant variation over time, suggesting a diurnal rhythm with increased levels in the morning. This rhythm is similar to those of adrenocorticotropin and beta-lipotropin (LPH) and reciprocal to the diurnal rhythm of pain sensitivity.     

The circadian rhythm of serum angiotensin-converting enzyme is disrupted in ascitic liver cirrhosis

An increase in morning fasting levels of plasma (P) renin activity (RA), aldosterone (A) and serum (S) angiotensin-converting enzyme (ACE) activity has been demonstrated in ascitic cirrhotic patients (ACP). Since both PRA and PA change biorhythmically in their time structure, the relationship of SACE activity with the components of the renin-angiotensin-aldosterone system (RAAS) was investigated in clinically healthy subjects (CHS) and ACP. Time-qualified data were chronobiologically analysed by means of the cosinor procedure to resolve and quantify the circadian rhythm (CR). The 24-hour mean levels of PRA, PA and SACE activity were found to be elevated in ACP as compared to CHS. The temporal variability of these analytes was found to be of periodic type along the 24-hour span in CHS, but not in ACP. The well-organized cyclicity in CHS is of relevant interest. PRA and PA cycles were found to phase in a clear antiparallelism with the SACE activity CR. The phase opposition may be, speculatively, related to the physiologic nature of ACE, whose activity is devoted to generate angiotensin II. The disappearance of SACE activity CR in ACP is in accordance with the abolition of PRA and PA cyclicity and suggests a role of liver in regulating the periodic time function of the RAAS and related components.     

Effects of various doses of captopril on plasma aldosterone concentrations in patients with essential hypertension

Various doses (5 mg, 12.5 mg and 25 mg) of angiotensin I converting enzyme inhibitor (SQ 14,255, captopril) were administered to 8 patients with essential hypertension on a three-crossover study design, and the time course of mean blood pressure (MBP), plasma renin activity (PRA), plasma angiotensin converting enzyme activity (ACE-A), plasma cortisol (PC) and plasma aldosterone (PA) were determined following administration of the drug. MBP fell in a dose dependent manner, and PRA showed a minor but significant increases in cases receiving 5 and 12.5 mg of the drug. A large and significant increase in PRA was observed following 25 mg of captopril. ACE-A was also reduced in a dose dependent manner. There was no difference between changes in PC at any of the three dose levels. The serum potassium concentration was determined before and 3 hr after 25 mg of captopril treatment and no significant change was observed. In spite of the dose dependent and theoretical changes in the above parameters, lowered responses of PA to each dose of the drug were shown in reverse order against an increasing dose. That is to say, the grade of fall in PA following 25 of captopril was smaller than that following the other doses of the drug, and 5 mg induced a greater decrease in PA than 12.5 mg. Based on these findings, the relatively high dose of captopril in the present study was apparently more effective in increasing some factors which suppressed reduction of PA by a fall in angiotensin II than a low dose of the drug.     

Effect of hydration on plasma volume and endocrine responses to water immersion

To determine the effect of hydration on the early osmotic and intravascular volume and endocrine responses to water immersion the hematocrit, hemoglobin, plasma renin activity (PRA), and plasma electrolyte, aldosterone (PA), and vasopressin (PVP) concentrations were measured during immersion following 24-h dehydration; these were compared with corresponding values following rapid rehydration. Six men and one woman (age 23-46 yr) underwent 45 min of standing immersion to the neck preceded by 45-min standing without immersion, first dehydrated, and then 105 min later after rehydration with water. Immersion caused an isotonic expansion of the plasma volume (P less than 0.001), which occurred independently of hydration status. Suppression of PRA (P less than 0.001) and PA (P less than 0.001) during both immersions also occurred independently of hydration status. Suppression of plasma vasopressin was observed during dehydrated immersion (P less than 0.001) but not during rehydrated immersion. It is concluded that plasma tonicity is not a factor influencing PVP suppression during water immersion.     

Diurnal variations in plasma testosterone concentrations in the male lesser mouse lemur (Microcebus murinus)

In 6 isolated adult male lesser mouse lemurs, concentrations of testosterone in plasma were determinated at 6-h intervals over a 24-h period. Blood samples were collected at monthly intervals and for a period of 12 months under natural photoperiod. In this nocturnal prosimian, there were no apparent diurnal changes in testosterone concentrations during the non-breeding season (autumn). During seasonal sexual activity (January-August), diurnal changes in testosterone concentrations were characterized by a significant rise during the light phase. The daily testosterone peak occurred about 8.5 h after sunrise from February to July, but at the beginning (January) or at the end (August) of the breeding season, the daily testosterone peak was displaced to the morning. A circannual testosterone rhythm occurred with the highest testosterone values in May/June and the lowest values 6 months later. The dramatic fall in testosterone concentrations after the summer solstice may be associated with a change in the peripheral metabolism of testosterone.