Genetic analysis of renin gene expression in rat adrenal gland

We examined the mechanism of the increased renin mRNA concentration in the adrenal glands of spontaneously hypertensive rats (SHR). In 52 female F2 rats (25 to 27 weeks of age) derived from SHR and Wistar-Kyoto rats, we determined blood pressure, renin mRNA concentration in the adrenal gland, plasma renin activity, plasma aldosterone concentration, and genotype of the renin gene. Eighteen of the F2 rats were fed a high salt (8%) diet for 14 days. The renin mRNA concentration in the adrenal glands showed a significant correlation with the genotype of the renin gene in the normal salt diet group (P <.0001), whereas this relationship was not observed in the high salt group. Multivariate analysis revealed that the plasma aldosterone concentration in the normal diet group was significantly explained (P=.0004, R2=.454) by plasma renin activity (P=.0005), the renin mRNA concentration in the adrenal gland (P=.0496), and the genotype of the renin gene (P=.0236). The SHR allele of the renin gene was associated with a lower aldosterone concentration. On the other hand, in the high salt diet group, only the genotype of the renin gene showed a significant relationship with plasma aldosterone concentration (P=.0237). Again, the SHR allele of the renin gene was associated with a lower aldosterone concentration. We can conclude that the higher renin mRNA concentration in the SHR adrenal glands is governed by the SHR allele of the renin gene or renin gene locus. The renin mRNA concentration in the adrenal gland exerts a minor influence on aldosterone synthesis. Paradoxically, the SHR allele of the renin gene or renin gene locus confers a lower rate of aldosterone synthesis at 25 to 27 weeks of age, the mechanism of which remains to be determined.     

Effect of bedrest on circadian rhythms of plasma renin, aldosterone, and cortisol

Previous studies of normal men after 5 d of bedrest showed that circulatory instability on head-up tilt or standing is preceded by increased plasma renin activity (PRA) at bedrest. In the present study, the circadian rhythms of PRA, aldosterone, and cortisol have been observed in five normal men on a constant diet. In ambulatory controls, PRA and aldosterone increased normally after standing. On the third morning of bedrest, PRA was higher than before, and at noon, PRA was higher than in standing controls. The nocturnal peaks of PRA resulting from episodic renin secretion during sleep were higher after bedrest. Plasma aldosterone was also increased by bedrest. The findings are compatible with the theory that intermittent beta-adrenergic nerve activity during sleep is increased after bedrest, but other factors, such as loss of body sodium and a lower plasma volume, may also be involved.     

The influence of dose and dose rate on the incidence of neoplastic disease in RFM mice after neutron irradiation

The effect of circadian rhythm and alterations in posture on plasma aldosterone concentration was studied in 13 patients with primary aldosteronism (six adenoma, five idiopathic hyperplasia, two carcinoma) to define the regulatory mechanism in each of these pathologic subtypes. Blood samples for aldosterone, cortisol, renin, and potassium concentrations were obtained every 4 h during prolonged recumbency (32 h) and upright posture (16 h). During recumbency, aldosterone and cortisol followed a normal circadian pattern in patients with adenoma and hyperplasia, with peak values at 0400-0800 h and the nadir at 1600-2400 h. Normalized aldosterone and cortisol values correlated significantly in both groups (adenoma r=+0.66, P less than 0.001; hyperplasia r=+0.42, P less than 0.01). With upright posture, aldosterone levels declined parallel to the normal circadian fall in cortisol in patients with adenoma (r=+0.68, P less than 0.001); whereas aldosterone levels increased in patients with hyperplasia parallel to small increments in renin (r=+0.65, P less than 0.001) and potassium (r=+0.64, P less than 0.001). During the administration of dexamethasone, aldosterone no longer correlated with cortisol in patients with adenoma but continued to correlate with renin during upright studies in patients with hyperplasia (r=+0.77, P less than 0.01). Aldosterone circadian rhythm was abnormal in patients with carcinoma and no effect of posture was noted. Unilateral adrenalectomy restored the normal postural relationship in four patients with adenoma. These studies suggest that aldosterone secretion is under continuous ACTH control regardless of posture in patients with adenoma, whereas persistent adrenal responsiveness to small increments in renin and/or potassium mediate the postural increase in plasma aldosterone in patients with hyperplasia. True adrenal autonomy occurs only in patients with adrenal carcinoma and when ACTH is suppressed in those with adenoma.     

Determination of sulindac and its metabolites in human serum by reversed-phase high-performance liquid chromatography using on-line post-column ultraviolet irradiation and fluorescence detection

OBJECTIVE: Data concerning the effect of angiotensin II (Ang II) on plasma angiotensinogen levels are conflicting. Although Ang II is reported to stimulate the biosynthesis of angiotensinogen, plasma angiotensinogen is often depleted by renin when the level of renin, and therefore Ang II, increases. In the present study we used the Ang II subtype 1 (AT1) receptor antagonist losartan to investigate whether rising plasma Ang II levels stimulate angiotensinogen production to counteract the falling plasma angiotensinogen levels caused by increasing renin activity in plasma. METHOD: Angiotensinogen was measured in plasma from two previously reported studies in which 6-week-old stroke-prone spontaneously hypertensive rats (SHRSP) or Dahl salt-sensitive (Dahl-S) rats were fed high-salt diets (4 and 8% sodium chloride, respectively) for 10-12 weeks with or without losartan. RESULTS: As reported previously, plasma renin was suppressed during the first 4 weeks of the high-salt diet but then paradoxically increased in both strains. When plasma renin increased, plasma angiotensinogen levels fell to 45 and 62% of the baseline value. The plasma renin concentration was negatively correlated with plasma angiotensinogen both in SHRSP and in Dahl-S rats (r = -0.76, P < 0.001 and r = -0.60, P < 0.001, respectively). In Dahl-S rats losartan treatment was associated with lower levels of plasma angiotensinogen but caused greater increases in plasma renin. When differences in renin were taken into account, plasma angiotensinogen levels were not different in losartan-treated and untreated Dahl-S rats. Similarly to Dahl-S rats, plasma angiotensinogen fell in SHRSP when renin increased, but SHRSP had higher plasma angiotensinogen levels during losartan treatment because plasma renin concentration was lower. CONCLUSION: The present study shows, in two strains of hypertensive rat, that an increase in plasma renin levels is associated with a fall in plasma angiotensinogen levels. Concurrent treatment with an Ang II AT1 receptor antagonist does not augment this fall, except to the extent that renin rises further. The results provide no evidence for a significant tonic stimulatory effect of Ang II on plasma angiotensinogen levels.     

Aldosterone and renin in liver cirrhosis with ascites

Supine plasma aldosterone and plasma renin activity were determined in patients with cirrhosis of the liver and ascites (n = 10). Most of the patients initially showed an increase in plasma aldosterone and plasma renin activity. However, values within the normal range were observed (plasma aldosterone, n = 3; plasma renin activity, n = 4). In the ascitic fluid renin activity could not be detected, whereas aldosterone concentrations correlated significantly with the respective plasma levels (r = 0.8, p less than 0.01). During therapy with spironolactone alone (n =2) or in combination with furosemide (n = 4), diuresis and natriuresis showed no correlation with changes in plasma aldosterone and/or plasma renin activity. Our results suggest that other factors than renin and aldosterone secretion may be important in the formation of ascites in patients with cirrhosis of the liver. In addition, the inverse correlation between mean arterial blood pressure and plasma renin activity (r = -0.65, p less than 0.05) found in our patients supports the assumption that the increase in renin secretion is probably induced by changes in (renal) hemodynamics.     

Mammotrophic activity in rat serum during the oestrous cycle, pregnancy and lactation

The mammotrophic activity of various serum samples was assessed on the mammary gland of pregnant rats, in organ culture. Insulin was added to the medium. Serum samples from virgin rats showed little activity, and variation in mammotrophic activity during the oestrous cycle was slight. During pregnancy a significant increase in proliferative activity was not seen during the first week, but around day 8-9 mammotrophic activity increased sharply. The activity showed maxima around days 12 and 19. A decrease in the activity between these maxima was not consistently observed. Mammotrophic activity was still present in sera collected during parturition, and 30 min after parturition. It had disappeared completely within 24 h. The mammotrophic factor detectable by organ culture in the serum of pregnant rats could be rat chorionic mammotrophin. Activity in the serum on day 0 and 1 of lactation was comparable to that of virgin rats, but some activity appeared on day 2. High actvities were foound frequently around day 4 to 6 of lactation. On other days the activity showed fluctuations without a definite pattern. Litter size was of minor importance but the combination of a larger litter size and fasting-overnight seemed to suppress the presence of mammotrophic activity in the serum. Nursing was important: after weaning the activity has disappeared, while renewed nursing after weaning resulted in the appearance of high levels of activity. The mitotic activity obtained with lactating rat serum in the culture was suppressed by addition of rabbit anti-rat prolactin serum to the medium. This suggests that the main mammotrophic factor detectable by organ culture in the serum of lactating rats, is prolactin.     

On the pathogenesis of Bartter's syndrome: report of studies in a patient with this disorder

A 25 year old male with features typical of Bartter's syndrome is described. Studies were performed to evaluate the pathogenesis of this disorder. In response to oral water loading the subject excreted free water normally. Normal renal sodium conservation was documented. Autonomy of the reninangiotensin-aldosterone system was excluded by demonstrating appropriate directional changes in plasma renin activity and aldosterone excretion in response to alterations in sodium and potassium intake. During aminoglutethimide inhibition of aldosterone synthesis the subject was able to maintain potassium balance at a normal serum potassium concentration on a potassium intake of 130 mEq/day which suggests that aldosterone is the major cause of the potassium wasting. Decreased vascular responses to intra-arterial infusions of angiotensin II and norepinephrine were documented in the absence of extracellular volume depletion. These findings argue against tachyphylaxis as the explanation for the vascular insensitivity and implicate a defect at some step in the sequence between agonist-receptor interaction and the contractile response. It is proposed that the vascular defect plays a primary role in the pathogenesis of the hyperreninemia by interrupting pressure-mediated inhibition of renin secretion and/or impairing direct feedback inhibition of renin secretion by angiotensin II. A unique finding in our case was the lack of a postural influence on plasma renin activity and plasma aldosterone. An accentuated plasma aldosterone circadian rhythm was observed independent of plasma renin activity and plasma potassium concentration. Dexamethasone suppression of ACTH reduced but did not abolish the circadian rhythm. Thus some factor in addition to plasma renin activity, potassium and ACTH appears to influence aldosterone secretion in this patient.     

Natriuresis after cardiopulmonary bypass: relationship to urodilatin, atrial natriuretic factor, antidiuretic hormone, and aldosterone

OBJECTIVE: Recent studies suggest that urodilatin from the kidneys rather than atrial natriuretic factor from the heart is the more important member of the family of natriuretic peptides involved in the normal regulation of renal sodium and water excretion. We thus examined the relationship between natriuresis, urodilatin, and atrial natriuretic factor in patients after cardiopulmonary bypass, a procedure known to increase levels of atrial natriuretic factor significantly. METHODS: Excretion rates of sodium and water were correlated with the excretion of urodilatin and with circulating levels of atrial natriuretic factor, antidiuretic hormone, aldosterone, and plasma renin activity during a period of 16 hours in 12 patients having had coronary artery bypass operations and with approximately a 400% elevation in levels of atrial natriuretic factor. RESULTS: Natriuresis did not correlate with atrial natriuretic factor, antidiuretic hormone, aldosterone, or plasma renin activity. Excretion rates of urodilatin, however, correlated significantly with excretion rates of sodium (r = 0.74, p = 0.03), urine flow (r = 0.83, p = 0.01), and with levels of serum sodium (r = 0.82, p = 0.01). CONCLUSION: These results suggest an important role for urodilatin, greater than that of atrial natriuretic factor, in the regulation of renal excretion of sodium and water after cardiopulmonary bypass surgery.     

Lyme carditis: a clinical presentation and long time follow-up

1. We evaluated the effects of the dietary restriction of sodium chloride on blood pressure and systemic calcium metabolism in 19 in-patients with essential hypertension (11 men and 8 women, mean age 49.9 +/- 12.1 years). 2. All patients received a high-sodium diet (250 mmol/day) for 1 week, followed by a low-sodium diet (10 mmol/day) for another week. Intake of potassium (100 mmol/day) and of calcium (15 mmol/day) were kept constant throughout the study. 3. Sodium restriction significantly reduced the mean blood pressure (from 114.0 +/- 1.9 to 105.0 +/- 13.7 mmHg, P < 0.01). Urinary calcium excretion was significantly reduced (from 5.1 +/- 2.4 to 2.2 +/- 1.0 mmol/day, P < 0.01). 4. The change in mean blood pressure after sodium restriction was not correlated with a change in any parameter of calcium metabolism [whole blood ionized calcium, plasma intact parathyroid hormone, or 1,25-(OH)2 vitamin D3]. 5. Plasma renin activity during a regular sodium diet, an index of renin status, was significantly and inversely correlated with the change in blood pressure during sodium restriction, but not with any change in the parameters of calcium metabolism. 6. We conclude that sodium restriction reduces blood pressure and decreases urinary calcium excretion. However, we observed no significant role of extracellular calcium concentration or of calciotropic hormone concentration in the mechanism of sodium sensitivity.     

Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1alpha, granulocyte-macrophage colony-stimulating factor, and interferon-gamma release from alveolar macrophages in asthma

In the present study, we examined denervation-induced changes in the sensitivity of hypothalamic postsynaptic serotonin1A (5-HT1A) receptor function with respect to changes in the dose-dependent elevation in plasma hormones [adrenocorticotropic hormone (ACTH), corticosterone, prolactin, oxytocin, prolactin, renin and vasopressin] by the 5-HT1A agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT). Rats received intracerebroventricular (i.c.v.) injections of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or vehicle (0.1% ascorbate in saline) 3 weeks before challenge with increasing doses of 8-OH-DPAT (0, 10, 50 or 200 micrograms/kg s.c.). The effectiveness of 5,7-DHT-induced destruction of serotonergic neurons was confirmed by a 93% reduction in [3H]paroxetine-labeled 5-HT uptake sites in the hypothalamus. No changes in basal levels of ACTH, corticosterone, oxytocin, prolactin, renin and vasopressin were observed in rats that received i.c.v. 5,7-DHT injections. The dose-response curves for 8-OH-DPAT-induced elevations of plasma corticosterone and prolactin levels were shifted to the left in rats treated with 5,7-DHT, whereas no significant difference in the ACTH dose-response curve was observed between rats treated with vehicle and rats treated with 5,7-DHT. In contrast, the maximal oxytocin response to 8-OH-DPAT was attenuated in rats treated with 5,7-DHT. A 5,7-DHT-induced decline in the synthesis of oxytocin could explain this phenomenon. Although 8-OH-DPAT did not increase plasma levels of renin or vasopressin in rats treated with vehicle, 8-OH-DPAT produced an elevation (75%) in plasma renin concentration but not in vasopressin levels in rats that received i.c.v. injections of 5,7-DHT. No change was observed in [3H]8-OH-DPAT labeled 5-HT1A receptors in the hypothalamus. In summary, denervation of hypothalamic serotonergic nerve terminals produces supersensitivity of some neuroendocrine responses to 8-OH-DPAT independent of changes in the density of hypothalamic 5-HT1A receptors.     

Effect of chronically infused adrenomedullin in two-kidney, one-clip hypertensive rats

The hypotensive effect of chronically infused adrenomedullin, a potent vasodilator peptide, was examined in conscious two-kidney, one-clip (2K-1C) hypertensive and sham-operated rats. They were infused with 1.0 microgram/h of synthetic human adrenomedullin for 14 days by means of osmotic minipumps. Control groups were infused on the same schedule with 0.9% saline. Systolic blood pressure was measured before and during the infusion. Plasma renin activity, aldosterone and human adrenomedullin concentrations were determined at day 14 of the infusion. A significant reduction of systolic blood pressure was observed in the adrenomedullin-infused 2K-1C rats at day 4, and systolic blood pressure remained significantly lower throughout the experiment compared to that of the control 2K-1C. A similar hypotensive effect was seen in the adrenomedullin-infused sham-operated rats. Both the plasma renin activity and aldosterone concentrations of the adrenomedullin-infused 2K-1C and sham groups were significantly reduced compared to those of the respective control, whereas, the plasma human adrenomedullin concentration in the adrenomedullin-infused groups was found to be within the physiological range. These findings demonstrated that chronically infused adrenomedullin had a hypotensive effect accompanied by significant reductions of plasma renin activity and plasma aldosterone concentration in 2K-1C hypertensive and sham-operated rats.     

Studies on new process procedures in plasma fractionation and industrial scale. III. Removal of precipitates by filtration through a horizontal leaf filter with centrifugal cleaning (Funda filter) as an alternative to tubular-bowl centrifuges

To study the eyes' role in maintaining the circadian rhythm in pituitary-adrenal function, 24-h patterns of corticosterone levels were compared in intact and blinded adult female rats. Rats were blinded by optic enucleation at approximately 80 days of age. Nonstress plasma corticosterone levels were determined fluorometrically in serial blood samples obtained from a tail vein at 4-h intervals for 44-h periods, 3 and 10 weeks after surgery. At 3 weeks after surgery, blinded and intact rats demonstrated comparable rhythms in corticosterone levels. At 10 weeks, steroid fluctuations in individual blinded rats still had an approximate 24-h periodicity. However, these fluctuations were no longer synchronized with the light-dark cycle or with those of other rats. These findings suggest that rats blinded as adults have a free-running pituitary-adrenal circadian rhythm.     

Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects

We have studied the effect of prolonged hyperinsulinemia and hyperglycemia on serum leptin levels in young nonobese males during 72-h euglycemic-hyperinsulinemic and hyperglycemic ( approximately 8.5 and 12.6 mM) clamps. Hyperinsulinemia increased serum leptin concentrations (by RIA) dose-dependently. An increase in serum insulin concentration of > 200 pM for > 24 h was needed to significantly increase serum leptin. An increase of approximately 800 pM increased serum leptin by approximately 70% over 72 h. Changes in plasma glucose concentrations (from approximately 5.0 to approximately 12.6 mM) or changes in plasma FFA concentrations (from < 100 to > 1,000 microM) had no effect on serum leptin. Serum leptin concentrations changed with circadian rhythmicity. The cycle length was approximately 24 h, and the cycle amplitude (peak to trough) was approximately 50%. The circadian leptin cycles and the circadian cycles of total body insulin sensitivity (i.e., GIR, the glucose infusion rates needed to maintain euglycemia during hyperinsulinemic clamping) changed in a mirror image fashion. Moreover, GIR decreased between Days 2 and 3 (from 11.4+/-0.2 to 9. 8+/-0.2 mg/kg min, P< 0.05) when mean 24-h leptin levels reached a peak. In summary, we found (a) that 72 h of hyperinsulinemia increased serum leptin levels dose-dependently; (b) that hyperglycemia or high plasma FFA levels did not affect leptin release; (c) that leptin was released with circadian rhythmicity, and (d) that 24-h leptin cycles correlated inversely with 24-h cycles of insulin sensitivity. We speculate that the close positive correlation between body fat and leptin is mediated, at least in part, by insulin.     

The renin-angiotensin-aldosterone system in mother and fetus at term

Plasma renin activity, renin substrate, angiotensin II, aldosterone and cortisol were measured concurrently and renin concentration calculated in plasma from mothers during labor and delivery, from cord and from newborn infants. The renin-angiotensin-aldosterone system was found strongly stimulated in both mother and fetus. The high values of plasma renin activity in fetus were due exclusively to the high renin concentrations the substrate concentration being normal. In the mother, however, the markedly elevated renin substrate resulted in a doubling of relative values of renin activity compared to renin concentration. Therefore gradients of renin and renin substrate across the placenta are established, but the resulting renin activity is similar on both sides and the levels of generated angiotensin II are also nearly indentical with a good correlation between these last parameters. Aldosterone is as elevated in mother as in fetus whereas cortisol, due to its binding to transcortin, is twice as high in mother as in fetus. No correlation was found between renin activity or concentration of angiotensin II and aldosterone or cortisol indicating that other factors controlling aldosterone are involved.     

Renin and aldosterone suppression in the antihypertensive action of clonidine

In 18 hypertensive patients receiving a constant (100 mEq/day) sodium diet, treatment with clonidine (0.3 mg/day for 5 days) decreased blood pressure in 11 patients with high and normal renin levels and 7 with low renin levels. The high and normal renin group had early and rapid reductions in blood pressure and plasma renin activity. In contrast, the low renin group had a more gradual hypotensive response and only a small absolute decrease in plasma renin. For all patients, pretreatment renin levels were related to the initial decrease in blood pressure but not to the reductions measured after 5 days. Thus, two mechanisms of action of clonidine are possible, one related to acute inhibition of the renin-angiotensin system in patients with high and normal renin levels and another that is independent of renin mechanisms and occurs in all hypertensive patients. In six additional patients with high renin levels induced by prior sodium depletion (10 mEq/day sodium diet), clonidine did not reduce blood pressure or renin, thus indicating that the suppressive action of this agent on renin pressor mechanisms occurs only in patients whose elevated renin levels are intrinsic to hypertension and unrelated to sodium depletion. Of the 18 patients receiving a normal sodium diet, 13 were classified as responding to treatment (decrease in both systolic and diastolic pressures of at least 10%). The five nonresponders had greater weight gain and higher values for aldosterone excretion. For all patients, there was a significant correlation between decrements in blood pressure and in aldosterone, suggesting that the countervailing effects of fluid accumulation on blood pressure in nonresponding patients resulted from a failure of aldosterone to be suppressed. Changes in aldosterone, in turn, correlated significantly with changes in renin. Thus, the antirenin effect of clonidine enhances its antihypertensive action not only by acutely ablating renin-angiotensin pressor mechanisms, but also by inhibiting aldosterone production and thereby minimizing longer-term reactive volume retention during treatment.     

Nocturnal blood pressure and relation to vasoactive hormones and renal function in hypertension and chronic renal failure

The purpose of this study was to assess the blood pressure profile and to measure vasoactive hormones in patients with essential hypertension (n=61), secondary hypertension (n=32) and chronic renal failure (n=32) matched with healthy control subjects (n=35), and to study the relationship between circadian changes in blood pressure and baseline levels of vasoactive hormones and renal function. Non-invasive, automatic blood pressure measurement was performed for 24 or 48 h. Venous plasma concentrations of renin, angiotensin II, aldosterone, arginine vasopressin, atrial natriuretic peptide and endothelin were measured. The mean 24-h blood pressure was higher in all groups of hypertensive patients than in control subjects. The nocturnal blood pressure fall was preserved in essential hypertension, in contrast to secondary hypertension in which it was attenuated. In the patients with chronic renal failure the 24-h mean blood pressure was the same as in the controls. Night-time blood pressure was higher among the chronic renal failure patients than in the control group, and the nightly blood pressure fall in both diastolic and systolic blood pressure was reduced. Plasma concentrations of renin activity, arginine vasopressin, atrial natriuretic peptide, aldosterone and endothelin were significantly increased in secondary hypertension and chronic renal failure, compared to essential hypertension and control subjects. Plasma angiotensin II was increased in chronic renal failure compared to essential hypertension and controls. Estimated creatinine clearance and nightly blood pressure dips were inversely correlated in essential and secondary hypertension, i.e. with a decreasing renal function both systolic and diastolic nightly blood pressure dips were gradually attenuated. In the whole group of patients the nightly systolic and diastolic blood pressure dips were negatively correlated to basal plasma renin activity, plasma aldosterone and atrial natriuretic peptide levels, i.e. the higher the basal plasma hormone level the lower the blood pressure dip. In conclusion, patients with essential hypertension have elevated but normally configured 24-h blood pressure profiles, and patients with different kinds of secondary hypertension have elevated 24-h blood pressure profiles and attenuated nightly systolic and diastolic blood pressure falls. The more the renal function is reduced and the more the plasma levels of renin and aldosterone are increased, the more the nocturnal fall in blood pressure is reduced. It is suggested that the attenuated or absent decrease in nocturnal blood pressure in secondary renal hypertension is caused by an abnormally increased secretion of vasoactive hormones and/or by so far unknown factors released from the diseased kidney.     

Changes in patterns of feeding activity, parotid secretory enzymes and plasma corticosterone in developing rats

The diet and feeding patterns of developing rats were determined from feed bin weight losses and analysis of stomach contents (details in a previous report). Parotid gland development in the same rats was assessed from the specific activities of the secretory enzymes alpha-amylase, RNase and DNase, with particular attention to the occurrence of circadian variations. The results indicate that during the first week post partum, rats suckle much more by day than by night but have no circadian cycles in their parotid glands. Between 10 and 20 days, there were no consistent cycles either in feeding activity or in parotid enzymes. The progressive change from milk to stock diet between 14 and 30 days appears to promote the maturation of the parotid gland. The halfway point in the dietary change at 21 days coincides with the onset of inversely related circadian cycles in feeding and the parotid enzymes. Premature weaning at 21 days accentuates both cycles and accelerates parotid maturation. The findings indicate that the physical consistency of the diet has an imporant regulatory role in the developmental patterns of feeding activity and parotid glands of rats, but they also hint that other dietary qualities may be involved. Chronologic fluctuations in plasma corticosterone suggest an intricate relationship among this hormone, feeding behavior, and parotid glands in developing rats.     

Prediction of serum IgG1 concentration in Holstein calves using serum gamma glutamyltransferase activity

We examined the relationship between serum gamma glutamyltransferase (GGT) activity and serum gamma immunoglobulin G (IgG1) concentration in Holstein calves. Blood samples were collected from calves aged 1 to 3 days. A follow-up sample was obtained from each calf 2, 7, or 15 days after the initial sampling. Serum GGT activity and IgG1 concentration were measured. Regression models were used to predict IgG1 concentration as a function of age and serum GGT activity measured 2, 7, or 15 days later. Serum GGT activity and calf age at the time of the second sample were directly related to serum IgG1 concentration in the initial sample in calves aged 3 to 17 days (r = .54) and in calves aged 3 to 10 days (r = .63). Models were used to estimate the serum GGT activity equivalent to a serum IgG1 concentration of 1,000 mg/dL. One-day-old calves should have serum GGT activities > 200 IU/L. Four-day-old calves should have serum GGT activities > 100 IU/L. One-week-old calves should have serum GGT activities > 75 IU/L. Calves with serum GGT activities < 50 IU/L should be classified as having failure of passive transfer.     

Plasma renin and aldosterone in thyroid diseases

The effect of thyroid hormones on the renin-angiotensin-aldosterone system has not been fully resolved. Highly specific immunoassays for measurement of renin, aldosterone, free T4 (fT4), free T3 (fT3) and ultrasensitive TSH enables a direct and more accurate measurement of these hormones. We investigated the relationship between plasma renin, aldosterone and thyroid hormones in the basal state and after intravenous frusemide. This is a cross-sectional study involving 37 patients with thyrotoxicosis, 42 rendered euthyroid with normal fT4, fT3 and TSH levels, 17 with euthyroid levels of fT4 and fT3 but suppressed TSH, and 11 with hypothyroidism. Basal plasma renin was significantly higher in thyrotoxicosis (63.4 +/- 9.8 microU/ml, mean +/- SEM) compared to euthyroid (32.7 +/- 4.4 microU/ml) and hypothyroid (26.7 +/- 9.8 microU/ml). Basal plasma renin for euthyroid with suppressed TSH (41.0 +/- 7.4 microU/ml) was significantly higher than hypothyroid (p = 0.02). Basal plasma aldosterones were not significantly different except for suppressed TSH (157.7 +/- 13 pg/ml), which was higher than normal (109.9 +/- 10.4 pg/ml; p = 0.04). Following frusemide, plasma renin and aldosterone were significantly increased in all groups. Plasma renin was highly correlated to fT3 (r = 0.405, p < 0.001), total T3 (r = 0.359, p < 0.001), fT4 (r = 0.331, p < 0.001) and TSH (r = 0.300, p < 0.001) in the basal state, but less to total T4 (r = 0.248, p < 0.01). Plasma renin correlated poorly to serum aldosterone (r = 0.212, p < 0.03). This study clearly showed that regulation of renin was mainly influenced by fT3, and that aldosterone response to frusemide was blunted in thyrotoxicosis despite normal electrolytes.     

Mineralocorticoids in the nephrotic syndrome of children

Free aldosterone, the aldosterone precursor 18-OH-corticosterone, and 18-OH-deoxycorticosterone as well as the aldosterone metabolites 18-glucuronide and tetrahydroaldosterone were measured by radioimmunoassay in the urine of 24 children with the nephrotic syndrome. In addition renin activity, aldosterone and corticosterone were measured in plasma. All children with manifest edema showed increased values of one or more of the measured aldosterone parameters indicating hyperaldosteronism. In non-edematous patients one or more parameters were increased in 9 of 16 patients. Free aldosterone, tetrahydroaldosterone and 18-OH-corticosterone proved to be the most sensitive urinary parameters for the detection of increased mineralocorticoid function. Free urinary aldosterone was correlated with sodium excretion and with serum albumin. The pathogenesis of hyperaldosteronism in the nephrotic syndrome and its role in the development of edema are discussed.