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G K Adler

Publications and source records attributed to G K Adler.

At least 19 recordsLinked to original sources
PubMed2006

Estradiol increases proteinuria and angiotensin II type 1 receptor in kidneys of rats receiving L-NAME and angiotensin II.

Prospective, placebo-controlled clinical trials suggest that estrogen may have adverse effects on the vascular system in women. The goal of this study was to determine if 17beta-estradiol (E2) would have adverse effects on the renovasculature in a rat model of renal injury characterized by low nitric oxide (NO) and high angiotensin II (AngII). We studied female Wistar rats that were sham-operated (sham), ovariectomized (OVX), or ovariectomized and replaced with E2 (OVX/E2). All rats were maintained on a high salt diet and renovascular injury was caused by treating rats with an inhibitor of NO synthase, N(omega)-nitro-L-arginine-methyl-ester (L-NAME), for 14 days, plus AngII on days 11 through 14. L-NAME/AngII treatment, as compared to placebo, caused proteinuria, glomerular injury, and fibrinoid necrosis of renal arterioles in sham-operated rats. Ovariectomy reduced L-NAME/AngII-induced renal damage, whereas E2 treatment increased L-NAME/AngII-induced damage in OVX rats. In rats treated with L-NAME/AngII, levels of AngII type 1 receptor (AT(1)R) protein were higher in the renal cortex of sham and OVX/E2 rats than in OVX rats. AT(1)R protein correlated with renal injury. E2 treatment also increased expression of AT(1)R mRNA. Thus, under conditions of low NO and high AngII, E2 exacerbated renal injury. E2-mediated increases in renal cortical AT(1)R expression may represent a novel mechanism for the adverse renovascular effects of estrogen.

Angiotensin II↗
PubMed2001

Circadian rhythms of women with fibromyalgia.

Fibromyalgia syndrome is a chronic and debilitating disorder characterized by widespread nonarticular musculoskeletal pain whose etiology is unknown. Many of the symptoms of this syndrome, including difficulty sleeping, fatigue, malaise, myalgias, gastrointestinal complaints, and decreased cognitive function, are similar to those observed in individuals whose circadian pacemaker is abnormally aligned with their sleep-wake schedule or with local environmental time. Abnormalities in melatonin and cortisol, two hormones whose secretion is strongly influenced by the circadian pacemaker, have been reported in women with fibromyalgia. We studied the circadian rhythms of 10 women with fibromyalgia and 12 control healthy women. The protocol controlled factors known to affect markers of the circadian system, including light levels, posture, sleep-wake state, meals, and activity. The timing of the events in the protocol were calculated relative to the habitual sleep-wake schedule of each individual subject. Under these conditions, we found no significant difference between the women with fibromyalgia and control women in the circadian amplitude or phase of rhythms of melatonin, cortisol, and core body temperature. The average circadian phases expressed in hours posthabitual bedtime for women with and without fibromyalgia were 3:43 +/- 0:19 and 3:46 +/- 0:13, respectively, for melatonin; 10:13 +/- 0:23 and 10:32 +/- 0:20, respectively for cortisol; and 5:19 +/- 0:19 and 4:57 +/- 0:33, respectively, for core body temperature phases. Both groups of women had similar circadian rhythms in self-reported alertness. Although pain and stiffness were significantly increased in women with fibromyalgia compared with healthy women, there were no circadian rhythms in either parameter. We suggest that abnormalities in circadian rhythmicity are not a primary cause of fibromyalgia or its symptoms.

Adult↗
PubMed2000

Aldosterone: a mediator of myocardial necrosis and renal arteriopathy.

To determine the role of aldosterone in mediating cardiovascular damage, we performed ablation/replacement experiments with aldosterone in a rat model of cardiac injury. Administration of angiotensin II and Nomega-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthesis inhibitor) to male rats drinking 1% saline caused hypertension, severe biventricular myocardial necrosis, proteinuria, and fibrinoid necrosis of renal and cardiac vessels. Removal of aldosterone by adrenalectomy or through administration of the selective aldosterone antagonist eplerenone markedly reduced the cardiac and renal damage without significantly altering blood pressure. Aldosterone infusion in adrenalectomized, glucocorticoid-replaced L-NAME/angiotensin II-treated animals restored damage. Thus, we identified aldosterone as a critical mediator of L-NAME/angiotensin II induced vascular damage through mechanisms apparently independent of its effects on systolic blood pressure.

Adrenalectomy↗
PubMed1999

Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome.

PURPOSE: To perform a detailed comparison of the hypothalamic-pituitary-adrenal axis and the sympathoadrenal system in women with and without fibromyalgia. SUBJECTS AND METHODS: Fifteen premenopausal women who met the 1990 American College of Rheumatology criteria for the diagnosis of fibromyalgia and 13 healthy, premenopausal women were enrolled. We measured baseline 24-hour urinary free cortisol levels and evening and morning adrenocorticotropic hormone (ACTH) and cortisol levels, performed stepped hypoglycemic hyperinsulinemic clamp studies in which serum glucose levels were decreased from 5.0 to 2.2 mmol/L, and compared the effects of infusions of placebo and ACTH. RESULTS: Women with fibromyalgia had normal 24-hour urinary free cortisol levels and normal diurnal patterns of ACTH and cortisol. There was a significant, approximately 30%, reduction in the ACTH and epinephrine responses to hypoglycemia in women with fibromyalgia compared with controls. Prolactin, norepinephrine, cortisol, and dehydroepiandrosterone responses to hypoglycemia were similar in the two study groups. In subjects with fibromyalgia, the epinephrine response to hypoglycemia correlated (P = 0.01) inversely with overall health status as measured by the fibromyalgia impact questionnaire. Graded ACTH infusion revealed similar increases in cortisol in women with fibromyalgia and healthy controls. CONCLUSIONS: Patients with fibromyalgia have an impaired ability to activate the hypothalamic-pituitary portion of the hypothalamic-pituitary-adrenal axis as well as the sympathoadrenal system, leading to reduced ACTH and epinephrine responses to hypoglycemia.

Adrenal Glands↗
PubMed1998

Tetanus toxoid stimulation of the hypothalamic-pituitary-adrenal axis correlates inversely with the increase in tetanus toxoid antibody titers.

In humans, endotoxin activates the hypothalamic-pituitary-adrenal (HPA) axis, and the resulting increase in cortisol modulates the immune response. There is little information on the HPA axis response to other antigens. We examined the effect of the protein antigen tetanus toxoid on HPA axis activity in 10 healthy, premenopausal women (aged 28.6 +/- 2.6 yr). Subjects received im injections of placebo and tetanus toxoid at 1600 h on consecutive days. Blood samples for ACTH and cortisol were obtained every half-hour from--1 to 6 h and at 8, 12, and 16 h after each injection. Compared to placebo, tetanus toxoid administration stimulated significant increases in plasma ACTH and serum cortisol, with the maximum cortisol increase of 1.6-fold occurring 4.5 h after drug administration. Urinary free cortisol increased 1.8-fold in the 8 h after tetanus toxoid administration compared to that after placebo administration. Additionally, there was a significant inverse correlation (r = 0.87; P < 0.005) between the tetanus toxoid-induced increase in serum cortisol and the increase in tetanus antibody levels measured 1 month postvaccination. Thus, administration of the protein antigen tetanus toxoid activated the HPA axis in healthy, premenopausal women. This activation of the HPA axis correlated inversely with the antibody response to tetanus toxoid.

Adrenal Glands↗
PubMed1996

Calcium modulation of adrenocorticotropin levels in women--a clinical research center study.

In vitro calcium modulation of anterior pituitary hormone secretion has been well described. In addition, several investigations performed in human subjects have documented modulation of the circulating levels of pituitary hormones by supraphysiological calcium concentrations. Recent data from our laboratory document the existence of an extracellular calcium-sensing receptor that is thought to mediate the effects of variations in extracellular calcium on the secretion of PTH and calcitonin. We have also demonstrated the presence of this receptor in pituitary-derived, ACTH-secreting AtT-20 cells as well as in the anterior pituitary of rats and mice. In the present study we investigated the effect on anterior pituitary hormone levels of variations in serum calcium within the physiological range. We serially measured serum levels of ionized calcium (Cai), ACTH, cortisol, TSH, and PRL during 90-min iv infusions (on separate days) of calcium, citrate, and dextrose in 10 healthy women with a mean age of 55 +/- 5 yr. During the calcium infusion, the serum Cai level increased significantly from 4.32 +/- 0.10 mg/dL at baseline to 4.86 +/- 0.08 mg/dL at completion (P = 0.002), and this change was accompanied by a significant increment in the serum ACTH level from 9.87 +/- 1.32 to 16.31 +/- 2.84 pg/mL (P = 0.0008). There was no change in the serum ACTH level during the citrate infusion despite significant decrements in serum Cai, nor were there changes in either Cai or ACTH during the dextrose infusion. Finally, changes in Cai did not alter TSH or PRL levels. In summary, our dynamic studies are the first to demonstrate an increase in baseline serum ACTH levels in response to physiological increments in Cai (i.e. increments within the normal range). This effect was specific for increments and not decrements in serum Cai and was selective for ACTH, as TSH and PRL levels did not change with any of the infusions.

Adrenocorticotropic Hormone↗
PubMed1996

Calcium-sensing receptor expression and regulation by extracellular calcium in the AtT-20 pituitary cell line.

A 120 kDa, G protein-coupled calcium-sensing receptor (CaR) was recently identified and cloned from bovine parathyroid and rat kidney. We report here that a similar calcium-sensing receptor is also present in rat and mouse pituitary as well as in the mouse pituitary cell line, AtT-20. Fragments (383-bp) of the extracellular domain of the calcium-sensing receptor from the AtT-20 cells and mouse pituitary were amplified by RT-PCR, sequenced, and found to be identical. By Northern blot analysis, AtT-20 cells expressed a major CaR mRNA transcript of 7.5 kb and three minor transcripts of 9.5, 4.0, and 1.5 kb. Except for the 9.5-kb species, these CaR transcripts were also found to be present in mouse kidney, where the 7.5-kb transcript was again the predominant form. The presence of the CaR protein in AtT-20 cells was documented directly by fluorescence immunocytochemistry using an antibody directed against the extracellular domain of the CaR. Exposure of AtT-20 cells to increasing extracellular calcium concentrations from 0.3 t 3 mM for 24 h resulted in a 2- to 4-fold increase in the levels of CaR mRNA, but not of the RNAs for beta-actin or POMC. The CaR appeared to be functional in AtT-20 cells, since acute increases in extracellular calcium between 2 and 5 mM induced increases in the cellular content of total inositol phosphates, cytosolic calcium, and cAMP. This report suggests that pituitary cells respond to changes in extracellular calcium via a G protein-coupled CaR.

Amino Acid Sequence↗
PubMed1994

Regulation of the ectopically expressed human glycoprotein alpha-subunit gene in the human hepatoma cell line NPLC.

The human glycoprotein alpha-subunit is the common subunit of the heterodimeric hormones CG (hCG), TSH, LH, and FSH. Human glycoprotein alpha-subunit is produced eutopically in placenta, pituitary, and choriocarcinoma and ectopically in a large variety of human tumors. We report ectopic glycoprotein alpha-subunit messenger RNA (mRNA) and peptide production in the human hepatoma cell line, NPLC. Neither hCG beta mRNA nor intact hCG peptide was detected. Antimetabolite regulation of glycoprotein alpha-subunit expression in NPLC cells resembled that found in choriocarcinoma cells in that it was stimulated by hydroxyurea. In addition, glycoprotein alpha-subunit mRNA expression and transcription in NPLC were stimulated by activators of the protein kinase A and C second messenger pathways, as well as by glucocorticoid. Glucocorticoid augmented glycoprotein alpha-subunit gene transcription by phorbol ester and forskolin, in contrast to its simultaneous inhibitory effect on phorbol ester activation of the CRH gene, which is also ectopically expressed in these cells. Glucocorticoid thus modulates the activation of these genes by phorbol ester in opposite directions, despite their identical cellular context. The NPLC cell line provides a new model for the study of human glycoprotein alpha-subunit gene regulation and free glycoprotein alpha-subunit secretion. In addition, it should be useful for investigating the role that specific cis-acting DNA sequences play in glucocorticoid modulation of gene induction by second messenger pathways.

Carcinoma, Hepatocellular↗
PubMed1993

Sodium restriction increases aldosterone biosynthesis by increasing late pathway, but not early pathway, messenger ribonucleic acid levels and enzyme activity in normotensive rats.

To determine whether changes in dietary sodium intake modify the early and/or late pathways of aldosterone biosynthesis, we studied in Sprague-Dawley rats the effect of sodium restriction on early (conversion of cholesterol to pregnenolone) and late (conversion of corticosterone to aldosterone) pathway activity and on the mRNA levels for the enzymes regulating these steps. Sodium restriction increased basal and angiotensin-II-stimulated aldosterone output from isolated zona glomerulosa cells by 5- to 9-fold. This increase in aldosterone output did not appear to be due to changes in the conversion of cholesterol to pregnenolone or in the mRNA levels of the early pathway enzyme, cholesterol side-chain cleavage cytochrome P-450. In contrast, sodium restriction increased the conversion of corticosterone to aldosterone 10-fold and increased by over 10-fold the mRNA levels of the late pathway enzyme aldosterone synthase. Sodium restriction had no effect on zona glomerulosa levels of 11 beta-hydroxylase mRNA. In two other normotensive rats, Dahl salt-resistant and Wistar Kyoto, sodium restriction again specifically increased aldosterone synthase mRNA without altering 11 beta-hydroxylase or cholesterol side-chain cleavage cytochrome P-450 mRNA levels. Thus, it appears that sodium restriction specifically increases late pathway aldosterone synthase mRNA levels, resulting in an increase in enzyme levels, followed by an increase in late pathway activity and an increase in aldosterone output.

Aldosterone↗
PubMed1992

Effects of glucocorticoid on corticotropin-releasing hormone gene regulation by second messenger pathways in NPLC and AtT-20 cells.

We have examined the regulation of the hypothalamic secretagogue CRH by glucocorticoid and the protein kinase-A and -C second messenger pathways in cultured cells. We show that the human primary liver carcinoma NPLC expresses the endogenous CRH gene. Dexamethasone reduced CRH mRNA levels by more than 90%, with half-maximal suppression at 5 nM. Phorbol ester treatment to activate the protein kinase-C pathway increased CRH mRNA levels up to 30-fold, whereas forskolin treatment to activate the protein kinase-A pathway had no effect. In coincubation experiments, dexamethasone completely suppressed phorbol ester-induced CRH mRNA levels in NPLC cells, maintaining them at the levels seen in untreated cells. We contrasted this regulation with the effects of glucocorticoid on CRH mRNA induction by forskolin in R1, a mouse anterior pituitary cell line (AtT-20) stably transfected with the human CRH gene. Dexamethasone suppressed forskolin-induced CRH mRNA levels by 70% in R1 cells, but only to levels that were still 10-fold greater than those in untreated cells. These results suggest that CRH induction in vivo by ligands that act via protein kinase-A may be less effectively suppressed by glucocorticoid feedback than CRH induction by ligands that act via protein kinase-C. This differential effect of glucocorticoid on CRH mRNA regulation could help explain the abnormal CRH production observed in clinical disorders such as anorexia nervosa and major depression.

Animals↗
PubMed1992

Dose effect of adrenocorticotropin on aldosterone and cortisol biosynthesis in cultured bovine adrenal glomerulosa cells: in vitro correlate of hyperreninemic hypoaldosteronism.

In some critically ill patients, aldosterone secretion is diminished despite hyperreninemia. These same patients demonstrate appropriately elevated plasma ACTH and cortisol levels. In addition, infusion of ACTH or angiotensin-II (AII) fails to elicit the normal aldosterone response, implying that the defect is at the level of the zona glomerulosa (ZG) cell. To test the hypothesis that elevated ACTH levels induce this defect, Percoll-purified bovine ZG cells were plated in serum-free defined medium and cultured for 5 days. On days 1-4, cells were exposed to various concentrations of ACTH for 1 h. On the fifth day of culture, half of the wells pretreated with ACTH were treated for 1 h with AII (10(-7) M); the other half of the wells received another dose of ACTH for 1 h. Additionally, cells were exposed to daily 1-h pulses of AII (10(-7) M) alone or in combination with ACTH (10(-8) M) for 5 days. Acutely dispersed bovine ZG cells showed dose-dependent increases in aldosterone when incubated with ACTH, potassium, or AII, with minimal cortisol production. Acutely dispersed bovine fasciculata cells produced no aldosterone, but demonstrated a dose-dependent cortisol response to ACTH and AII, but not potassium. On day 1 of culture, the ZG cells demonstrated a significant (P less than 0.001 in all cases) dose-related increase in aldosterone secretion in response to ACTH. However, continued daily pulsation with ACTH resulted in a dose-dependent decrease in aldosterone secretion, with a concomitant dose- and time-related rise in cortisol production. Indeed, ACTH-induced cortisol production in ZG became similar to ACTH-induced cortisol production in zona fasciculata cells. The addition of AII to the daily ACTH pulse did not significantly alter the aldosterone or cortisol response patterns to ACTH alone. In contrast, ZG cells treated with AII alone for 5 days showed a minimal change in cortisol production and no reduction in aldosterone production until day 4. Northern blot analysis of total RNA isolated from ZG cells pulsed with ACTH for 5 days demonstrated a parallel dose-dependent increase in 17 alpha-hydroxylase mRNA, which did not occur in cells pulsed with AII alone. These in vitro results suggest that elevated ACTH levels over time induce 17 alpha-hydroxylase activity in ZG cells, thereby shifting steroid biosynthesis from an aldosterone-producing to a cortisol-producing pathway. It is likely that the chronically elevated ACTH levels in critically ill patients induce a similar change in ZG cell biosynthesis, resulting in their hyperreninemic hypoaldosterone state.

Adrenocorticotropic Hormone↗
PubMed1992

Protein kinase-C activation increases the quantity and poly(A) tail length of corticotropin-releasing hormone messenger RNA in NPLC cells.

We have studied the effect of protein kinase-C activation on the regulation of CRH gene expression in the human hepatoma cell line NPLC/PRF/5 (NPLC), the only cell line known to express the endogenous CRH gene. Incubation of NPLC cells with 100 nM 12-O-tetradecanoyl phorbol 13-acetate (TPA), a phorbol ester that activates protein kinase-C, resulted in a rapid (1-h) and prolonged (72-h) increase in CRH mRNA levels, with the maximum increase of 16-fold observed at 24 h. In addition, TPA treatment increased the size of CRH mRNA by approximately 100 nucleotides. This size increase, which was blocked by protein synthesis inhibitors, occurred within 1 h of TPA addition and lasted at least 8 h, with a return toward the baseline size by 24 h. Structural analysis of CRH mRNA revealed two poly(A) addition sites and, as found in human placenta, multiple transcription start sites. The increase in CRH mRNA size was not due to changes in the sites of either transcription initiation or poly(A) addition, but, rather, to a 3-fold increase in the length of the poly(A) tail itself. The ability of TPA to increase CRH mRNA levels in NPLC cells suggests that the protein kinase-C second messenger pathway may be involved in the physiological regulation of CRH gene expression. Increases in CRH mRNA poly(A) tail length potentially may influence CRH mRNA stability or translatability and, thus, may represent a general mechanism by which the protein kinase-C pathway can influence gene expression.

Anisomycin↗
PubMed1990

Regulated expression of the human corticotropin releasing hormone gene by cyclic AMP.

The factors controlling the expression of the hypothalamic neuropeptide, corticotropin releasing hormone (CRH), are poorly understood. We have used a mouse anterior pituitary cell line, AtT-20, permanently transfected with the human CRH gene as a model for studying the regulation of the CRH gene by cyclic AMP. Previously, we demonstrated that in this system the CRH gene is correctly expressed and appropriately negatively regulated by glucocorticoids. Treatment of five CRH-producing cell lines with an activator of adenylate cyclase (forskolin, 0.1-50 microM for 24 h) caused a dose-dependent and specific increase in the amount of CRH mRNA and radioimmunoassay-detectable CRH peptide secreted into the medium. Ribonuclease protection analysis revealed that the CRH gene was transcribed from multiple transcriptional initiation sites located over several hundred nucleotides. Forskolin treatment resulted in a specific increase in the CRH mRNA transcripts initiating from one of these many transcriptional start sites.

Animals↗
PubMed1988

Expression and dexamethasone regulation of the human corticotropin-releasing hormone gene in a mouse anterior pituitary cell line.

The factors controlling the expression of corticotropin-releasing hormone (CRH), a hypothalamic neuropeptide involved in the regulation of ACTH secretion, are poorly understood partly because a suitable in vitro model is lacking. To study the regulation of CRH gene expression, an 8-kilobase (kb) DNA fragment containing the entire human CRH gene as well as approximately 6 kb of 5' sequence and 0.8 kb of 3' sequence was isolated from a lambda Charon 4A human genomic library and introduced into a mouse anterior pituitary cell line, AtT-20, by CaPO4 transfection with a neomycin-selectable marker. Approximately 10% of the neomycin-resistant lines stably expressed the CRH gene and secreted radioimmunoassay-detectable CRH into culture media at levels greater than 100 pg/ml. By Southern blot analysis the 8-kb DNA fragment containing the CRH gene had been incorporated intact into the AtT-20 genome. In each CRH-producing strain, but not in the parent AtT-20 cell line, we detected by Northern blot analysis an RNA species that hybridized to two radioactive cRNA probes specific for either the 5' or 3' portion of CRH mRNA, and that co-migrated with placental CRH mRNA. Dexamethasone treatment for 24-96 h caused a specific decrease in CRH mRNA and peptide levels of 40-50% in the five CRH-producing cell lines with half-maximal suppression at approximately 10(-9) M dexamethasone, indicating that CRH gene expression is negatively regulated by glucocorticoids. Thus, we have established an in vitro model suitable for studying in detail those cis- and trans-acting factors which regulate CRH gene expression.

Animals↗
PubMed1988

Characterization and gestational regulation of corticotropin-releasing hormone messenger RNA in human placenta.

Corticotropin-releasing hormone (CRH), a hypothalamic neuropeptide involved in the regulation of ACTH secretion, has been detected by RIA in extracts of human placenta. We wished to determine whether this immunoreactive substance is a product of CRH gene expression in the placenta. We have found authentic human CRH (hCRH) mRNA in human placental tissue that is similar in size to hypothalamic CRH mRNA. Furthermore, the transcriptional initiation site for placental hCRH mRNA is identical to that previously predicted for hypothalamic hCRH mRNA, 23-26 nucleotides downstream from a canonical promoter element. Placental hCRH mRNA increases more than 20-fold in the 5 wk preceding parturition, in parallel with a rise in placental hCRH peptide content. These data strongly suggest that the hCRH gene is expressed in the placenta and that this expression changes dramatically during gestation.

Base Sequence↗
PubMed1987

Influence of infused hypertonic saline on the response to insulin-induced hypoglycemia in man.

We studied the influence of a hypertonic saline infusion on the counterregulatory response to insulin-induced hypoglycemia in nine normal men. When given hypertonic saline, the men had less hypoglycemia in response to insulin, both acutely and in the recovery phase (P less than 0.01), and released 34% more glucagon (P less than 0.05) than when they were water loaded. The total integrated ACTH, cortisol, epinephrine, norepinephrine, and GH responses to hypoglycemia were similar after saline and water loading. After the saline load, the mean plasma vasopressin level rose from 11.0 +/- 2.2 (+/- SEM) to 20.9 +/- 2.9 pg/mL in response to insulin-induced hypoglycemia. In contrast, after the water load, vasopressin levels were undetectable (less than 2 pg/mL) and they increased only to 2.6 +/- 0.4 pg/mL with hypoglycemia. There was a significant positive correlation between basal plasma vasopressin and nadir glucose concentrations and a significant negative correlation between basal plasma vasopressin and the integrated fall in glucose after insulin administration (P less than 0.01 and P less than 0.025, respectively). The difference in the glycemic response to insulin may be related to the high vasopressin levels after saline loading, which could, either directly and/or through enhanced glucagon release, increase hepatic glucose production and thus limit the hypoglycemic response to insulin.

Adrenocorticotropic Hormone↗
PubMed1987

Changes in adrenal responsiveness and potassium balance with shifts in sodium intake.

Dietary sodium modulates the aldosterone response to angiotensin, but available evidence does not indicate whether there is a gradual change in adrenal responsiveness with intermediate sodium intakes or a sharp shift from a low to a high responsive level at some threshold sodium intake. Nine normal subjects received angiotensin II infusions while in balance on five levels of sodium intake over two orders of magnitude, 3 to 300 mEq sodium per day. Basal plasma renin activity, plasma aldosterone and plasma angiotensin II concentrations gradually fell as dietary sodium intake increased. The adrenal was quite sensitive to the state of sodium balance since a shift in sodium intake of as little as 20 mEq (e.g. 10 to 30 mEq/day) induced a significant change in basal plasma aldosterone. Adrenal responsiveness to infused angiotensin varied inversely with the log of urinary sodium excretion over the entire range of sodium intake, indicating that there is a gradual modulation of adrenal responsiveness with changes in dietary sodium. In addition, despite a constant dietary potassium intake, serum potassium gradually fell from 4.55 +/- .06 to 3.98 +/- .07 mEq/l, (P less than 0.02), as sodium intake increased, partly due to increased urinary potassium excretion (mean cumulative potassium loss of 129 mEq). Thus, changes in potassium balance may be important in modulating the sodium-associated variation in aldosterone secretion.

Adrenal Glands↗