Changes In Aldosterone Levels Research Articles

Clinical significance of endocrine disorders in the development of early vascular aging in males with abdominal obesity and concomitant arterial hypertension: An observational cohort study

Background. Visceral obesity is a risk factor in the development of metabolic and endocrine disorders leading to arterial hypertension and cardiovascular complications. Their early predictors include increased vascular stiffness and early vascular aging. The current literature lacks studies into the effects of changes in testosterone, cortisol, and aldosterone levels in serum on vascular stiffness and the development of early vascular aging in patients with visceral obesity. Objective. To determine the relationship between hypercortisolemia, hyperaldosteronemia, and hypotestosteronemia and vascular stiffness and the presence of early vascular aging in male patients with visceral obesity. Methods. An observational cohort study of 78 males aged 35–45 years (mean age 38.1 ± 6.5 years) diagnosed with abdominal obesity and grade 1 arterial hypertension was conducted. The mean waist circumference ranged 105.5 ± 6.9 cm; systolic and diastolic blood pressure ranged 152.5 ± 5.0 and 92.5 ± 5.0 mm Hg, respectively. The vascular age of the studied patients (n = 78) comprised 44.1 ± 6.2 years, which was statistically higher than their passport age (р < 0.001). The studied patients were divided into subgroups according to both total testosterone (< 12.1 nmol/l in subgroup 1A (n = 49) and ≥ 12.1 nmol/L in subgroup 1B (n = 29)) and cortisol in the evening saliva portion (> 4.5 nmol/L in subgroup 2A (n = 24) and ≤ 4.5 nmol/L in subgroup 2B (n = 24)). All the patients completed the study. To assess the hormonal status, the total testosterone sex steroid-binding globulin (SSBP) and insulin in morning serum samples were investigated. Insulin resistance was assessed based on the NOMA-IR index. The concentration of total testosterone was determined by enhanced chemiluminescence (Ortho-Clinical Diagnostics, J&J); the SSBP and insulin levels were determined by delayed fluorescence. Aldosterone content was determined by radioimmunoassay; free cortisol and testosterone were measured by luminescent LIA. Free and bioavailable testosterone concentrations in serum were calculated using an online calculator (issam.ch/freetesto.htm). The cardio-ankle vascular index (CAVI) was determined using a VaSera VS-15000N device, which automatically calculated the vascular age. Statistical analysis was performed using the Statistica 10.0 Windows package (StatSoft, Inc., USA). Results. The vascular age of patients with hypogonadism was statistically significantly ( р < 0.001) higher than their passport age and the vascular age in males without hypogonadism. The CAVI and vascular age were also statistically significantly higher in males with functional hypercorticism (р < 0.001) compared with a subgroup of patients without hypercorticism. The vascular age and CAVI increased with an increase in the salivary cortisol concentration 2200 (r = 0.5; р < 0.05) and decreased with an increase in the salivary cortisol level 900 (r = –0.5; р < 0.05). These parameters decreased with an increase in serum aldosterone obtained in the morning (r = –0.4; p < 0.05) and increased with an increase in serum aldosterone in the evening (r = 0.4; p < 0.05). In 23% (n = 18), an inversion of the daily rhythm of cortisol production was observed; in these patients, salivary cortisol levels of 2200 exceeded salivary cortisol levels of 900. The vascular age of patients with the inversion of cortisol production (49.4 ± 4.4 years) was statistically significantly ( р < 0.001) different from that of patients with normal changes in salivary cortisol concentrations (41.9 ± 4.9 years). CAVI was also higher (р < 0.001) in males with inverted fluctuations in salivary cortisol levels (7.51 ± 0.62) compared to those with normal diurnal rhythm (6.45 ± 0.69). The results of aldosterone evaluation revealed that 17% of the patients (n = 13) had higher aldosterone levels in the evening serum portion compared to the morning serum portion. In these patients, the vascular age (45.8 ± 5.1 years) was higher ( р < 0.001) than that in males with normal physiologic changes in aldosterone levels (41.6 ± 5.7 years). A similar pattern was observed when comparing vascular stiffness indices. Thus, the CAVI in men with inverted changes in aldosterone concentration (6.9 ± 0.8) was significantly higher ( р < 0.001), compared to that in men with physiological changes in blood aldosterone levels (6.4 ± 0.8). Conclusion. Endocrinologic disorders in male patients with visceral obesity and concomitant arterial hypertension (functional hypogonadism, functional hypercorticism, inverted daily rhythms of cortisol and aldosterone production) contribute to the development of early vascular aging by increasing vascular stiffness.

Serum Aldosterone as Predictor of Progression of Coronary Heart Disease in Patients Without Signs of Heart Failure After Acute Myocardial Infarction.

Introduction: In patients with acute myocardial infarction (AMI) early risk assessment of development of complications is of great importance. It is proven that aldosterone level has a major role in progression of cardiovascular pathology. Aim: Determination of influence of aldosterone plasma level in the progression of heart disease in patients without signs of heart failure after AMI. Material and Methods: Research included 207 patients, hospitalized in the acute phase of myocardial infarction, and who were divided into two groups: 127 patients with no clinical signs of heart failure and 60 patients with heart failure. Results: The serum aldosterone concentration was 73.4% higher in the group of decompensated patients, 128 pg/mL (75.4-236 pg/mL) in decompensated and 73.7 pg/mL (42.7 -115.25 pg/mL) in compensated. In the group of compensated patients, changes in aldosterone levels showed a statistically significant effect on the incidence of post-infarction angina (p=0.0001) as well as reinfarction (p=0.009). There is a connection between changes in aldosterone plasma level and positive stress test (p=0.012). Conclusion: In patients with AMI, elevated serum aldosterone level can be prognostic factor of the progression of coronary heart disease, development of heart failure, as well of development of post-infarction angina, myocardial reinfarction and pathological finding on the stress test.

The effect of renal denervation in an experimental model of chronic renal insufficiency, The REmnant kidney Denervation In Pigs study (REDIP study)

BackgroundRenal denervation (RDN) is a promising therapeutic method in cardiology. Its currently most investigated indication is resistant hypertension. Other potential indications are atrial fibrillation, type 2 diabetes mellitus and chronic renal insufficiency among others. Previous trials showed conflicting but promising results, but the real benefits of RDN are still under investigation. Patients with renal insufficiency and resistant hypertension are proposed to be a good target for this therapy due to excessive activation of renal sympathetic drive. However, only limited number of studies showed benefits for these patients. We hypothesize that in our experimental model of chronic kidney disease (CKD) due to ischemia with increased activity of the renin–angiotensin–aldosterone system (RAAS), renal denervation can have protective effects by slowing or blocking the progression of renal injury.MethodsAn experimental biomodel of chronic renal insufficiency induced by ischemia was developed using selective renal artery embolization (remnant kidney porcine model). 27 biomodels were assessed. Renal denervation was performed in 19 biomodels (denervated group), and the remaining were used as controls (n = 8). The extent of renal injury and reparative process between the two groups were compared and assessed using biochemical parameters and histological findings.ResultsViable remnant kidney biomodels were achieved and maintained in 27 swine. There were no significant differences in biochemical parameters between the two groups at baseline. Histological assessment proved successful RDN procedure in all biomodels in the denervated group. Over the 7-week period, there were significant increases in serum urea, creatinine, and aldosterone concentration in both groups. The difference in urea and creatinine levels were not statistically significant between the two groups. However, the level of aldosterone in the denervated was significantly lower in comparison to the controls. Histological assessment of renal arteries showed that RDN tends to produce more damage to the arterial wall in comparison to vessels in subjects that only underwent RAE. In addition, the morphological damage of kidneys, which was expressed as a ratio of damaged surface (or scar) to the overall surface of kidney, also did not show significant difference between groups.ConclusionsIn this study, we were not able to show significant protective effect of RDN alone on ischemic renal parenchymal damage by either laboratory or histological assessments. However, the change in aldosterone level shows some effect of renal denervation on the RAAS system. We hypothesize that a combined blockade of the RAAS and the sympathetic system could provide more protective effects against acute ischemia. This has to be further investigated in future studies.

Changes in plasma aldosterone and electrolytes levels, kidney epithelial sodium channel (ENaC) and blood pressure in normotensive WKY and hypertensive SHR rats following gonadectomy and chronic testosterone treatment

We hypothesized that testosterone-induced increase in blood pressure involve changes in aldosterone levels and expression of epithelial sodium channel (ENaC) in the kidneys. MethodsOvariectomized female normotensive Wistar Kyoto (WKY) and Spontaneous hypertensive (SHR) rats were given six weeks treatment with testosterone via subcutaneous silastic implant. The rats were anesthetized and mean arterial pressure (MAP) was measured via direct cannulation of the carotid artery. Animals were sacrificed and kidneys were removed and subjected for α, β and γ-ENaC protein and mRNA expression analyses by Western blotting and Real-time polymerase chain reaction (qPCR), respectively. Distributions of α, β and γ-ENaC proteins in kidneys were observed by immunofluorescence. Plasma testosterone, aldosterone, electrolytes, osmolality, urea and creatinine levels were determined by biochemical assays. Analysis were also performed in non-testosterone treated orchidectomized and sham-operated male WKY and SHR rats. ResultsTreatment of ovariectomized female WKY and SHR rats with testosterone causes increased in MAP but decreased in plasma aldosterone, sodium (Na+), osmolality and expression and distribution of α, β and γ-ENaC subunits in the kidneys. Orchidectomy decreased the MAP but increased plasma aldosterone, Na+, osmolality and α, β and γ-ENaC expression and distribution in the kidneys of male WKY and SHR rats. ConclusionsDecreased in plasma aldosterone, Na+ and ENaC levels in kidneys under testosterone influence indicated that testosterone-induced increased in MAP were not due to increased plasma aldosterone and ENaC levels in kidneys, and thus the testosterone effect on MAP likely involve other mechanisms.

Method development and validation of liquid chromatography-tandem/mass spectrometry for aldosterone in human plasma: Application to drug interaction study of atorvastatin and olmesartan combination.

In the present investigation, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed for the quantification of aldosterone (ALD) a hormone responsible for blood pressure in human plasma. The developed method was validated and extended for application on human subjects to study drug interaction of atorvastatin (ATSV) and olmesartan (OLM) on levels of ALD. The ALD in plasma was extracted by liquid-liquid extraction with 5 mL dichloromethane/ethyl ether (60/40% v/v). The chromatographic separation of ALD was carried on Xterra, RP-Column C18 (150 mm× 4.6 mm × 3.5 μm) at 30°C followed by four-step gradient program composed of methanol and water. Step 1 started with 35% methanol for first 1 min and changed linearly to 90% in next 1.5 min in Step 2. Step 3 lasted for next 2 min with 90% methanol. The method finally concluded with Step 4 to achieve initial concentration of methanol that is, 35% thus contributing the total method run time of 17.5 min. The flow rate was 0.25 mL/min throughout the process. The developed method was validated for specificity, accuracy, precision, stability, linearity, sensitivity, and recovery. The method was linear and found to be acceptable over the range of 50-800 ng/mL. The method was successfully applied for the drug interaction study of ATSV + OLM in combination against OLM treatment on blood pressure by quantifying changes in levels of ALD in hypertensive patients. The study revealed levels of ALD were significantly higher in ATSV + OLM treatment condition when compared to OLM as single treated condition. This reflects the reason of low effectiveness of ATSV + OLM in combination instead of synergistic activity.

Renal compensation to chronic hypoxic hypercapnia: downregulation of pendrin and adaptation of the proximal tubule

The molecular basis for the renal compensation to respiratory acidosis and specifically the role of pendrin in this condition are unclear. Therefore, we studied the adaptation of the proximal tubule and the collecting duct to respiratory acidosis. Male Wistar-Hannover rats were exposed to either hypercapnia and hypoxia [8% CO(2) and 13% O(2) (hypercapnic, n = 6) or normal air (controls, n = 6)] in an environmental chamber for 10 days and were killed under the same atmosphere. In hypercapnic rats, arterial pH was lower than controls (7.31 +/- 0.01 vs. 7.39 +/- 0.01, P = 0.03), blood HCO(3)(-) concentration was increased (42 +/- 0.9 vs. 32 +/- 0.24 mM, P < 0.001), arterial Pco(2) was increased (10.76 +/- 0.4 vs. 7.20 +/- 0.4 kPa, P < 0.001), and plasma chloride concentration was decreased (92.2 +/- 0.7 vs. 97.2 +/- 0.5 mM, P < 0.001). Plasma aldosterone levels were unchanged. In the proximal tubule, immunoblotting showed an increased expression of sodium/bicarbonate exchanger protein (188 +/- 22 vs. 100 +/- 11%, P = 0.005), confirmed by immunohistochemistry. Total Na/H exchanger protein expression in the cortex was unchanged by immunoblotting (119 +/- 10 vs. 100 +/- 11%, P = 0.27) and immunohistochemistry. In the cortex, the abundance of pendrin was decreased (51 +/- 9 vs. 100 +/- 7%, P = 0.003) by immunoblotting. Immunohistochemistry revealed that this decrease was clear in both cortical collecting ducts (CCDs) and connecting tubules (CNTs). This demonstrates that pendrin expression can be regulated in acidotic animals with no changes in aldosterone levels and no external chloride load. This reduction of pendrin expression may help in redirecting the CNT and CCD toward chloride excretion and bicarbonate reabsorption, contributing to the increased plasma bicarbonate and decreased plasma chloride of chronic respiratory acidosis.

Review: Relationship between Erythropoietin Administration and Alterations of Renin-Angiotensin-Aldosterone

The effect of erythropoietin (EPO) administration on the responsiveness of the renin-angiotensin-aldosterone system (RAAS) has not been established. Because patients with chronic kidney disease (CKD) require EPO for their management as CKD progresses, it is important to ascertain whether EPO treatment alters the RAAS. If EPO administration stimulates renin-angiotensin or aldosterone (ALDO) this intervention would mediate cardiovascular and renal injury, and consequently promote cardiovascular events and/or exacerbate the progression of renal disease. We reviewed the available publications investigating the effects of EPO on the RAAS. In CKD patients following EPO administration plasma renin activity (PRA) was unchanged in all three and ALDO was not altered in the two studies in which it was determined. In end-stage renal disease (ESRD) patients undergoing dialysis following EPO administration, four studies reported a decrease in PRA levels whereas the remaining nine disclosed no change in PRA levels. The changes in ALDO levels after EPO administration in ESRD patients were discrepant with two studies reporting an increase, two reporting a decrease and the remaining three disclosing no change.

Low-dose nitric oxide inhibition produces a negative sodium balance in conscious dogs.

Nitric oxide modulates renal hemodynamics and salt and water handling. Studies on the latter have provided conflicting results, however. Electrolyte and water balances were therefore studied in 28 beagles for 4 d, to determine the various effects of nitric oxide synthase (NOS) inhibition on renal function. The dogs were chronically equipped with aortic occluders to reduce renal perfusion pressure (RPP), bladder catheters, and catheters for measurements of RPP and mean arterial BP. A swivel system allowed free movement within the kennels. In a first set of experiments, a nonpressor dose of L-Nomega-nitroarginine (LN) (3 microg/min per kg body wt) was administered, to prevent increases in mean arterial BP and thus pressure effects on renin release and natriuresis. Remarkably, the nonpressor dose of LN caused a negative sodium balance. The natriuretic effect may involve reduced plasma renin activity, reduced aldosterone concentrations, and increased atrial natriuretic peptide concentrations. Changes in aldosterone levels, however, were the only parameters to parallel the time course of sodium excretion. In a second set of experiments, a sodium-retaining challenge was elicited by reduction of RPP. Dogs without NOS inhibition escaped sodium retention during RPP reduction after 2 d ("pressure escape"). LN neither ameliorated nor aggravated the sodium-retaining effect of reduced RPP, nor did it compromise the accomplishment of pressure escape. In conclusion, inhibition of NOS with a low dose of LN results in a reduction of total-body sodium. This effect mainly relies on reduced aldosterone concentrations. Furthermore, LN does not change the regulatory response to long-term RPP reduction.

Differential regulation of CHIF mRNA by potassium intake and aldosterone.

The channel-inducing factor (CHIF) is an epithelial-specific transmembrane protein, which is induced by aldosterone in distal colon (but not in kidney) and can evoke K+ conductance in Xenopus oocytes. The current study examined the possibility that CHIF participates in maintaining K+ balance by assessing its regulation during variations in K+ intake. In adrenal-intact rats, high-K+ diet stimulated, whereas K+ deficiency downregulated, CHIF mRNA both in kidney and colon. The downregulation of CHIF observed in rats fed a low-K+ diet for different periods of time closely correlated with a decrease in plasma K+ but also with changes in aldosterone levels. To differentiate between the two, modulation of CHIF has been studied in adrenalectomized rats with and without corticosteroid supplementation. These experiments have demonstrated that a low-K+ intake suppresses CHIF mRNA, irrespective of aldosterone level. On the other hand, the upregulation evoked by a high-K+ load is apparent only in adrenal-intact rats. This is despite the fact that infusing rats with aldosterone and corticosterone does not increase the expression of this mRNA in kidney. These findings may suggest a role for CHIF in preserving K+ balance.

Influence of Dietary Sodium and Other Factors on Plasma Aldosterone Concentrations and in Vitro Properties of the Lower Intestine in House Sparrows (Passer Domesticus)

ABSTRACT House sparrows ( Passer domesticus) had plasma aldosterone concentrations of about 180pgml−1 while maintained on a low-sodium diet (LS, 0.1mequiv Na+ ingested per day), 135pgml−1 on a sodium intake of 0.9mequivday−1 (high-salt diet, HS) and 45pgml−1 on a Na+ intake of 3.8mequivday−1 (high-salt diet with saline drinking water, HSS). The plasma concentration of aldosterone changed to the LS or the HS level within 1 day of switching from the HS or the LS diet, respectively. Neither dehydration (22h, 14.5% loss in body mass) nor brief periods of stress (1–5min of handling) caused a change in circulating levels of aldosterone. The electrical properties of the lower intestine acclimated to the different sodium intakes with a time course similar to that of the changes in aldosterone levels. On the LS diet, the lower intestine generated an electrical potential difference (PD) of 5mV (lumen negative) and a short-circuit current (Isc) of about 50 μA cm−2; these were consistently inhibited by amiloride (resulting in a lumen-positive PD) and were stimulated by glucose or amino acids (leucine and lysine) in about half of the tissues. In HS birds, the PD and Isc were abolished and the effects of glucose and amino acids were reduced, but amiloride still caused a significant change in transmural PD (to a mucosa-positive value). These properties resemble those of the chicken coprodeum more than they do those of chicken colon, although the tissues tested were from the mid-region of the large intestine and their histology resembled that of colon. Sparrows tested immediately upon capture from the wild had plasma aldosterone levels not significantly different from those of birds on the LS diet, which is consistent with the known diet of this species. However, Isc was higher and tissue resistance was lower in wild birds compared with low-salt birds in the laboratory, perhaps indicating the influence of other hormones in addition to aldosterone.

Renal actions of atrial natriuretic factor: modulation of effect by changes in sodium status and aldosterone

To examine the effect of changes in Na status on the renal response to atrial natriuretic factor (ANF), human ANF-(99-126) was infused into the renal artery of conscious sheep while Na replete, Na depleted, or Na loaded. The natriuretic response to ANF was attenuated during Na depletion and enhanced in Na-loaded animals. To demonstrate that the enhancement or attenuation of response was related to Na status rather than to the initial level of Na excretion, aldosterone was infused into the renal artery for 2 h to decrease Na excretion to a level inappropriately low for the animal's Na status (and not different from Na-depleted animals), and they were again challenged with ANF. Their response to ANF, however, was not significantly different from that in normal Na-replete animals but was significantly greater than that observed in Na-depleted animals. Similarly, Na-loaded animals treated with aldosterone had control Na excretion in the Na-replete range; however, their response to ANF was not significantly different from that of Na-loaded animals. The response to ANF was enhanced in sheep treated with aldosterone for 48 h, consistent with Na retention and hypervolemia, secondary to aldosterone treatment. The study demonstrates that Na status or some associated physiological parameter is an important determinant of the natriuretic response to ANF. The present series of experiments demonstrate that changes in aldosterone levels per se are not a determinant of the natriuretic response to ANF.

Physiological mechanisms associated with ovulation prediction using the CUE Ovulation Predictor.

It has been shown that monitoring of salivary electrical resistance (SR) enables prediction of ovulation several days in advance, since a peak in SR is seen 5-6 days before the LH peak. This paper explores physiological mechanisms that may account for this change. The pathway whereby oestrogen stimulates aldosterone (ALDO) secretion acting through the renin-angiotensin system was considered. It is shown that this mechanism would only result in increasing SR as oestrogen values rise during the follicular phase and therefore is not an explanation of the SR peak and declining SR 5-6 days before the LH peak. The reported trend of sodium in milk of ovulating women parallels that of SR. It is shown that these changes are most likely to be due to a similar change in aldosterone levels. A possible role for adrenocorticotrophic hormone (ACTH) in causing the changes in aldosterone is discussed and supported with data from other independent studies as well as with preliminary data obtained from two normally ovulating subjects. Peaks in ACTH, ALDO and SR were coincidental and occurred 6 days before the LH peak. The temporal relationship observed among these variables suggest that ACTH, by affecting ALDO, modifies salivary electrolytes and hence SR.

Central serotonergic stimulation of aldosterone secretion.

Serotonin stimulates aldosterone secretion both in vitro and in vivo, and serotonin antagonism decreases plasma aldosterone levels in patients with idiopathic aldosteronism. This study was designed to assess the effects of the serotonin precursor, 5-hydroxytryptophan (5HTP), upon aldosterone secretion in man, and to determine whether stimulatory effects of 5HTP are mediated through the central nervous system. Oral 5HTP, administered as a single 200-mg dose, increased plasma aldosterone levels from 4.7 +/- 0.6 to 13.3 +/- 2.8 ng/dl in dexamethasone-pretreated, normal volunteers. Peripheral inhibition of decarboxylation of 5HTP, achieved by pretreatment with carboxydopa, 25 mg three times daily for 3 d, significantly increased the stimulatory effects of 5HTP on aldosterone levels (P less than 0.001). No change in aldosterone levels occurred in subjects who received placebo after pretreatment with dexamethasone and carboxydopa. Increased aldosterone was not accompanied by increases in plasma levels of renin activity, potassium, or ACTH. Plasma levels of 5HTP were markedly increased by carboxydopa pretreatment, but peak plasma levels of serotonin were not significantly altered. Four patients with idiopathic aldosteronism all had an increase in plasma aldosterone levels after 5HTP administration, whereas the response in four patients with aldosterone-producing adenoma was variable. Incubation of isolated human and rat adrenal glomerulosa cells with serotonin resulted in increased aldosterone secretion by both sets of cells, whereas 5HTP was ineffective in stimulating aldosterone secretion in vitro. We conclude that central serotonergic pathways are involved in the stimulation of aldosterone induced by administration of 5HTP. This mechanism may be an important etiologic factor in the hypersecretion of aldosterone that occurs in patients with idiopathic aldosteronism.

Immunoreactive acth level in the human pituitary and blood serum during prenatal development

The occurrence of a single-phase circadian rhythm in the content of cortisole, 11-deoxycortisole, 17-hydroxypregnenolone, 17-hydroxyprogesterone, pregnenolone and progesterone in the blood plasma of hamadryas baboons was established by radioimmunoassay with peak levels early in the morning and minimum ones in the evening. The time course of changes in aldosterone levels in the intact animals significantly differs from that in the adapted ones. The maintenance of animals under other ecological conditions results in the decreased levels of all steroids studied and in significant changes in circadian rhythms of the content of cortisol precursors.

Effect of simultaneous potassium and saline loading on plasma aldosterone levels.

To assess the relative importance of the renin-antiotensin system and potassium in the acute regulation of aldosterone secretion in the salt depleted state, normal subjects were infused with an asotonic saline solution containing potassium chloride (KCl) and the responses compared to the infusions of isotonic saline (500 ml/h) and KCl alone (20 mEq K+/h). Subjects were studied recumbent in balance on a 10 mEq sodium/100 mEq potassium diet. The rates of infusing saline and potassium were selected to produce comparable but opposite effects on the levels of plasma aldosterone. As plasma renin activity (PRA) declined and plama potassium increased during the combined saline-KCl infusions, plasma aldosterone levels appeared to be the arithmetic sum of the changes in these parameters. In fact, the calculated changes in aldosterone levels per unit change in PRA or potassium from each infusion alone, correlated well with the observed levels, further supporting an additive relationship. These data support the concept that in the salt depleted state the renin-angiotensin system and potassium are equally important in the acute regulation of plasma levels of aldosterone.

Na+ transport by rabbit urinary bladder, a tight epithelium.

By in vitro experiments on rabbit bladder, we reassessed the traditional view that mammalian urinary bladder lacks ion transport mechanisms. Since the ratio of actual-to-nominal membrane area in folded epithelia is variable and hard to estimate, we normalized membrane properties to apical membrane capacitance rather than to nominal area (probably 1 muF approximately 1 cm2 actual area). A new mounting technique that virtually eliminates edge damage yielded resistances up to 78,000 omega muF for rabbit bladder, and resistances for amphibian skin and bladder much higher than those usually reported. This technique made it possible to observe a transport-related conductance pathway, and a close correlation between transepithelial conductance (G) and short-circuit current (Isc) in these tight epithelia. G and Isc were increased by mucosal (Na+) [Isc approximately 0 when (Na+) approximately 0], aldosterone, serosal (HCO-3) and high mucosal (H+); were decreased by amiloride, mucosal (Ca++), ouabain, metabolic inhibitors and serosal (H+); and were unaffected by (Cl-) and little affected by antidiuretic hormone (ADH). Physiological variation in the rabbits' dietary Na+ intake caused variations in bladder G and Isc similar to those caused by the expected in vivo changes in aldosterone levels. The relation between G and Isc was the same whether defined by diet changes, natural variation among individual rabbits, or most of the above agents. A method was developed for separately resolving conductances of junctions, basolateral cell membrane, and apical cell membrane from this G--Isc relation. Net Na+ flux equalled Isc. Net Cl- flux was zero on short circuit and equalled only 25% of net Na+ flux in open circuit. Bladder membrane fragments contained a Na+-K+-activated, ouabain-inhibited ATPase. The physiological significance of Na+ absorption against steep gradients in rabbit bladder may be to maintain kidney-generated ion gradients during bladder storage of urine, especially when the animal is Na+-depleted.

The effect of magnesium deficiency on serum aldosterone in rats fed two levels of sodium

Rats were fed 47 (deficient) and 606 ppm (adequate) magnesium with either 2,100 or 14,000 ppm sodium. Serum corticosterone and aldosterone levels were determined by randoimmunoassay in six rats from each treatment group killed on days 7, 14, and 28 of consumption of the experimental diets. Serum corticosterone levels were moderately, but not significantly, decreased in magnesium deficient animals. Serum aldosterone levels increased over time in the rats fed the lower sodium diet with adequate magnesium and were further elevated in magnesium deficient animals. In sodium loaded rats the increase in aldosterone levels in magnesium deficiency was less and occurred later. Retention and urinary excretion of sodium and potassium did not appear to be affected by magnesium status or the serum concentration of aldosterone. Possible mechanisms underlying the changes in aldosterone levels of magnesium depleted animals are discussed with reference to the known effects of magnesium deficiency on physiological functions.