Aldosterone

T clinical, laboratory, and ultrasonography data in the remainder. herapeutic paracentesis may be associated with an impairment in circulatory function, which is manifested by a marked increase in the degree of activity of Abbreviations used in this paper: ALDO, plasma aldosterone; ANF, plasma atrial natriuretic factor; CI, cardiac index; FHVP, free hepatic the renin-angiotensin and sympathetic nervous systems. venous pressure; HBF, hepatic blood flow; HR, heart rate; HVPG,

Steroid actions on brain tissue have been implicated in processes such as blood pressure regulation and neurodegeneration, including the progression of Alzheimer's disease (AD). mRNAs from all of the genes required for de novo synthesis from cholesterol of aldosterone and corticosterone (equivalent to cortisol in humans) have been identified in rat brain, together with abundant steroid hormone receptors, but the situation in human brain requires clarification. We used real-time RT-PCR to assess whether transcription of 13 steroid-associated genes occurs in human hippocampus and cerebellum, and to identify whether transcription of these genes is significantly altered in cases of AD. Frozen post-mortem samples of hippocampus and cerebellum from patients with AD (nZ7) and age-matched controls free from neurological disease at the time of death (nZ9) were used. We found all of the genes under investigation to be transcribed within normal and AD hippocampus and cerebellum except for CYP11B1 (11b-hydroxylase), CYP11B2 (aldosterone synthase) and CYP17 (17a-hydroxylase). No significant differences in mRNA levels were observed between the AD tissue and the equivalent control tissue, although significant regional differences in gene transcription were observed between hippocampus and cerebellum in AD and control samples. The absence of key mRNAs from human hippocampus and cerebellum rules out the de novo generation of aldosterone, cortisol or the sex steroids within these regions. However, the pattern of gene expression does suggest that the mineralocorticoid 11-deoxycorticosterone can be generated de novo. There is no evidence of a link between AD and altered steroid biosynthesis within human hippocampus and cerebellum.

Following phase I studies of docetaxel and cisplatin in patients with non-small-cell lung cancer, the recommended doses of docetaxel were different for elderly (Ն 75 years) and non-elderly (Ͻ 75 years) patients. To elucidate the mechanism of the difference, the pharmacokinetics of docetaxel and cisplatin were investigated in two phase II studies separately conducted in elderly and non-elderly patients.

We have assessed the potential for myocardial ischaemia during laparoscopic cholecystectomy in 16 otherwise healthy patients. Continuous ambulatory ECG monitoring was commenced 12 h before operation and continued for 24 h after operation. The neuroendocrine stress response was assessed by measuring plasma concentrations of adrenaline and noradrenaline, human growth hormone, cortisol, renin and aldosterone, and prolactin, at specified times during surgery. Acute ST segment changes in the ECG occurred in only two patients. These episodes were independent of creation of pneumoperitoneum and changes in position. Acute intraoperative increases in MAP were noted during insufflation of carbon dioxide and reverse Trendelenburg positioning (P : 0.05). A four-fold increase in plasma concentrations of renin and aldosterone was noted after pneumoperitoneum and reverse Trendelenburg positioning (P 9 0.05).

The primary product of the renin gene is preprorenin. A signal peptide sorts renin to the secretory pathway in juxtaglomerular cells where it is released into the circulation to initiate the renin-angiotensin system cascade. In the brain, transcription of renin occurs from an alternative promoter encoding an mRNA starting with a new first exon (exon 1b). Exon 1b initiating transcripts skip over the classical first exon (exon 1a) containing the initiation codon for preprorenin. Exon 1b transcripts are predicted to use a highly conserved initiation codon within exon 2, producing renin, which should remain intracellular, because it lacks the signal peptide. To evaluate the roles of secreted and intracellular renin, we took advantage of the organization of the renin locus to generate a secreted renin (sRen)-specific knockout, which preserves intracellular renin expression. Expression of sRen mRNA was ablated in the brain and kidney, whereas intracellular renin mRNA expression was preserved in fetal and adult brains. We noted a developmental shift from the expression of sRen mRNA in the fetal brain to intracellular renin mRNA in the adult brain. Homozygous sRen knockout mice exhibited very poor survival at weaning. The survivors exhibited renal lesions, low hematocrit, an inability to generate a concentrated urine, decreased arterial pressure, and impaired aortic contraction. These results suggest that preservation of intracellular renin expression in the brain is not sufficient to compensate for a loss of sRen, and sRen plays a pivotal role in renal development and function, survival, and the regulation of arterial pressure. (Hypertension.

Objective: To study the changes in blood volume and hormones controlling sodium and water homeostasis after infusions of 0.9% saline, Gelofusine (4% succinylated gelatin in 0.7% saline, weight-average molecular weight 30 kD), and Voluven (6% hydroxyethyl starch in 0.9% saline, weight-average molecular weight 130 kD) in healthy volunteers.

Background: It is not known whether physical exercise increases daily proteinuria in patients with proteinuric nephropathies, thus accelerating progression of the renal lesion. This study evaluates the acute effects of physical exercise on proteinuria in young adults with immunoglobulin A (IgA) nephropathy. Methods: Changes induced by intense physical exercise on quantitative and qualitative proteinuria were evaluated in basal conditions and after 10 days of ramipril therapy in 10 patients with IgA nephropathy, normal glomerular filtration rate (GFR), proteinuria between 0.8 and 1.49 g/24 h, and "glomerular" microhematuria before and after the end of a maximal treadmill Bruce test (B-test). The basal study also was performed in 10 age-and sex-matched healthy volunteers. Results: At rest, GFR averaged 141 ؎ 23 mL/min; it increased by 16.3% ؎ 3.3% (P < 0.005) and 7.1% ؎ 1.6% at 60 and 120 minutes after the B-test, respectively. At rest, GFR-corrected proteinuria averaged protein of 0.76 ؎ 0.21 mg/min/100 mL GFR; it increased to 1.55 ؎ 0.28 mg/min/100 mL GFR after 60 minutes (P < 0.001) and declined to 0.60 ؎ 0.11 mg/min/100 mL GFR at 120 minutes after the end of the B-test. The pattern of urinary proteins remained unchanged, as did microhematuria. Daily proteinuria was not different from the basal value on the day of the B-test. After ramipril therapy, patients showed a reduction in GFR, but no change in daily GFR-corrected proteinuria, pattern of urinary proteins, or hematuria. Conclusion: The increase in proteinuria after exercise in our patients is significant and is not prevented by ramipril therapy, but lasts less than 120 minutes. Therefore, it cannot modify daily proteinuria. Thus, these data do not support the need to reduce acute physical activity in patients with nonnephrotic renal diseases. Am J Kidney Dis 44:257-263.

Calcium channel blockers are widely used antihypertensives. Mineralocorticoid receptor antagonists are also used to treat hypertension and heart failure. We report here that a number of widely used dihydropyridine class calcium channel blockers are able to inhibit aldosterone-induced activation of mineralocorticoid receptor. These dihydropyridines varied in the extent of their effect on mineralocorticoid receptor, with nimodipine and felodipine the most potent and amlodipine the least. In contrast, both diltiazem and verapamil, nondihydropyridine calcium channel blockers, had no effect on mineralocorticoid receptor. These dihydropyridines compete with aldosterone for binding and block aldosterone-induced coactivator recruitment to mineralocorticoid receptor. The mineralocorticoid receptor S810L mutant, which is activated by steroidal mineralocorticoid receptor antagonist such as eplerenone, is inhibited by these drugs. Furthermore, nimodipine decreased aldosterone-induced expression of the mineralocorticoid receptor target gene epithelial sodium channel gamma subunit in adrenalectomized rats, demonstrating that dihydropyridine calcium channel blockers can function as mineralocorticoid receptor antagonists in vivo. Molecular modeling indicates that dihydropyridines dock into the ligand binding domain of mineralocorticoid receptor in a consensus pose that partially overlaps with steroidal mineralocorticoid receptor antagonists. Together, our data suggest that, in addition to their calcium channel blocking activity, a number of dihydropyridine calcium channel blockers also have mineralocorticoid receptor antagonist activity at high doses, a finding which may thus prove useful for the design of novel antihypertensive drugs in the future. (Hypertension. 2008;51:742-748.) Key Words: calcium channel blockers Ⅲ aldosterone Ⅲ mineralocorticoid receptor antagonist Ⅲ dihydropyridine

Background and objective: The laboratory has a critical role to play in the screening and diagnosis of primary aldosteronism. This review highlights some of the important analytical considerations and the new developments in the determination of aldosterone and renin.

Genetic polymorphisms in the Catechol O-Methyltransferase (COMT) gene have been linked to increased pain sensitivity in a number of studies. A literature search was performed to integrate the current knowledge of the gene, its regulation, influences of the polymorphisms upon enzyme function and its population distributions. Assessment also includes the current knowledge of the enzyme structure, isoforms, function and metabolic activities, substrates, and products. Other gene polymorphisms which may influence the components involved within the COMT enzymatic reaction, such as folate metabolism polymorphisms and cofactor availability, were also briefly assessed. A review of enzyme agonists and antagonist and how these may influence the enzymes functions, its substrates and products is undertaken in an attempt to understand the potential interactions between COMT and factors that may influence enzyme activity in the presence or absence of the COMT polymorphic forms.

Once considered rare, primary aldosteronism (PAL) is now regarded as the commonest potentially curable and specifically treatable form of hypertension. At Greenslopes Hospital Hypertension Unit (GHHU), the decision in 1991 to screen all (and not just hypokalemic or resistant) hypertensives by aldosterone/renin ratio (ARR) testing led to a 10-fold increase in detection rate of PAL and four-fold increase in removal rate of aldosterone-producing adenomas (APAs). The GHHU/Princess Alexandra Hospital Hypertension Unit PAL series stands at 977 patients and 250 APAs removed with hypertension cured in 50-60% (remainder improved). Reliable detection requires that interfering medications are withdrawn (or their effects considered) before ARR measurement, and reliable methods (such as fludrocortisone suppression testing) to confirm PAL. Adrenal venous sampling is the only dependable way to differentiate APA from bilateral adrenal hyperplasia. Genetic testing has facilitated detection of glucocorticoid-remediable, familial PAL. Identification of mutations causing the more common familial variety described by GHHU in 1991 should further aid in detection of PAL.

P. L  V. P. Induction of Cardiac Fibrosis by Aldosterone. Journal of Molecular and Cellular Cardiology (2000) 32, 865-879. An intracardiac aldosterone system which responds to short-and long-term physiological stimuli has been described. This cardiac generated aldosterone has possibly autocrine or paracrine actions.

A rethinking of current heat-acclimation strategies is required as most research and advice for improving physiological strain in the heat includes maintaining hydration using long-term acclimation protocols (>10 days). Furthermore, these strategies have tended to use untrained and moderately trained participants. Therefore, the aims of this review were to (i) investigate the effectiveness of short-term heat acclimation (STHA) with moderately and highly trained athletes; (ii) determine the importance of fluid regulatory strain, which has a thermally independent role in heat adaptation; (iii) assess the impact of STHA on a marker of thermotolerance (inducible heat-shock protein 70 [HSP70]); and (iv) provide further information on the decay of acclimation to heat. The review suggests that 5-day STHA is effective, and adaptations may be more pronounced after fluid regulatory strain from a dehydration-acclimation regimen. Furthermore, highly trained athletes may have similar physiological gains to those who are less trained using STHA. However, research has tended to focus on untrained or moderately trained participants and more information is required for highly trained populations. HSP70 response is upregulated across STHA. This indicates increased thermotolerance and protective adaptive change that may indicate HSP70 response as a useful marker of heat acclimation. Physiological adaptations after heat acclimation are relatively short term and may vanish only a few days or

Neonatal hypertension is an uncommon but important complication of intensive care management. The aims of this study were to identify in neonates with hypertension: antenatal and postnatal risk factors; aldosterone and renin levels; and report on outcome in early infancy. The study involved a retrospective review of neonates diagnosed with systemic hypertension from January 2001 to December 2005. Demographic data, risk factors, laboratory investigation, and follow-up data at 3-6 months of age were collected. Of the 2,572 newborn infants included, 34 (1.3%) had neonatal hypertension. Gestational age and birth weight and length were significantly lower in infants with hypertension. The median postnatal age at diagnosis of systemic hypertension was 5.0 days. Antenatal steroid administration, maternal hypertension, umbilical arterial catheter, postnatal acute renal failure, patent ductus arteriosus, indomethacin treatment and chronic lung disease were associated with the development of ...

Aldosterone, a steroid hormone with mineralocorticoid activity, is far more than merely a salt-and-water hormone. Aldosterone has a number of non-classical, mineralocorticoid receptor (MR)-mediated actions, including tissue remodeling, modulation of vascular tone and stimulating inflammation and fibrosis, which may fuel progression of end organ damage. Aldosterone breakthrough during blockade of the renin-angiotensin aldosterone system (RAAS) may explain why this treatment regimen only confers partial cardiovascular and renal protection. Of major interest, aldosterone is deleterious only if inappropriately high for its sodium status i.e. high aldosterone and high sodium. The mechanism of sodium dependence of aldosterone-induced renal and cardiovascular damage continues to fascinate. Aldosterone excess increases sodium and fluid retention and consequently increases blood pressure, which, in turn, mediates target organ damage. Moreover, blood pressure independent effects play a role with dissociation of low circulating and high tissue aldosterone levels during high sodium intake and possibly enhanced MR signaling. MR blockade is a valuable strategy, which has potency to halt the progressive end organ damage as observed during current treatments. In heart failure, MR blockade on top of RAAS blockade reduces hard clinical endpoints. Despite encouraging results on the intermediate endpoint proteinuria, long-term data on the efficacy and safety of MR blockade in preventing dialysis and/or cardiovascular endpoints in chronic kidney disease are still lacking. It is obligatory that future clinical studies on the effects of MR blockade on endorgan damage take into account the sodium status.

The aims of this study were to propose a bioindicator organism, the newt Triturus carnifex, for the assessment of toxicological impact of thiophanate methyl in the Campania region (Italy) and the possible adverse activity on the adrenal gland. In the acute toxicity study, experimental groups of T. carnifex were exposed to 2.40, 4.80, 9.60 and 19.20 μg/L tap water of thiophanate methyl for 2 days; the LD 50 was found to be 9.60 μg/L. To evaluate the effects on the adrenal gland, newts were exposed to a dose of 25% of the LD 50 2 days for 8 days. The ultrastructural features of the tissues as well as the serum levels of aldosterone, corticosterone, norepinephrine (NE) and epinephrine (E) were evaluated. The number of secretory vesicles in the chromaffin cells appeared significantly decreased, whereas NE and E serum levels appeared strongly increased. Moreover, corticosterone and aldosterone serum levels appeared significantly reduced. The results suggest that: 1) T. carnifex has the features of an ideal bioindicator, due to its high sensitivity to thiophanate methyl, 2) thiophanate methyl acts as endocrine disruptor, affecting the adrenal gland at very low doses, 3) thiophanate methyl may be toxic for nontarget organisms, such as newts.

Measurement of serum aldosterone is clinically important in the diagnosis of hypertension. While isotope dilution gas chromatography-mass spectrometry (ID-GC-MS) provides reliable results, it requires derivatization and is lengthy and time-consuming. Detection by liquid chromatography-mass spectrometry (LC-MS) is a potentially superior method. The analysis utilizes 0.5 mL of serum. The samples were extracted with dichloromethane-ether. The extract was evaporated to dryness and aldosterone was analyzed by LC-MS/MS operating in the negative mode ESI after separation on a reversed-phase column. Aldosterone was also measured by RIA. The calibration curves for analysis of serum aldosterone exhibited consistent linearity and reproducibility in the range of 60-3000 pmol/L. Interassay CVs were 4.3-7.5% at aldosterone concentrations of 97-993 pmol/L. The lower limit of quantitation (LOQ) was 30 pmol/L (signal to noise ratio = 10). The mean recovery of the analyte added to serum ranged from 95 to 102%. The regression equation by LC-MS/MS (x) and RIA (y) method was: y = 1.33x + 185 (r = 0.95; n = 124). Sensitivity and specificity of the LC-MS/MS method for serum aldosterone offer advantages over GC-MS by eliminating derivatization. The novel method is rapid, reliable and simple to perform with a routine LC-MS/MS spectrometer. The sensitivity is adequate for patient samples. Aldosterone concentrations reported by nonextraction RIA were consistently higher than those produced by LC-MS/MS.

Cardiac hypertrophy arises as a response of the heart to many different pathological stimuli that challenge its work. Regardless of the initial pathologic cause, cardiac hypertrophy shares some characteristics resulting from a genetic reprogramming of several proteins. Recent studies point to Ca 2+ as a key signaling element in the initiation of this genetic reprogramming. In fact, besides its important role in excitation-contraction coupling, Ca 2+ regulates cardiac growth by activation of Ca 2+ -dependent transcription factors. This mechanism has been termed excitation-transcription (ET) coupling. Some information about cardiac ET coupling is being gathered from the analysis of cardiac hypertrophy development, where two Ca 2+ dependent enzymes are key actors: the Ca 2+ /calmodulin kinase II (CaMKII) and the phosphatase calcineurin, both activated by Ca 2+ /Calmodulin. In this review we focus on some neurohormonal signaling pathways involved in cardiac hypertrophy, which could be ascribed as activators of ET coupling, for instance, adrenergic stimulation and the renin-angiotensin-aldosterone system. -adrenergic receptor ( -AR) produces cAMP, which directly, (through cAMP response element) or indirectly (through activating Epac) induces cardiac hypertrophy. 1 AR and angiotensin receptor type 1 are Gq protein coupled receptors, which when activated, stimulate phospholipase C producing inositol 1,4,5 triphosphate (IP3) and diacylglycerol (DAG). IP3 promotes elevation of [Ca 2+ ] in the nucleus, activating CaMKII/MEF2 (myocyte enhancer factor 2) pathway and may indirectly induce Ca 2+ entry through transient receptor potential channels (TRPC). Other TRPC channels are activated by DAG. Ca 2+ entry activates calcineurin/NFAT hypertrophic signaling. By promoting L-type Ca 2+ channel expression, aldosterone may also have an important role in the genetic reprogramming during hypertrophy.

Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3′,5′-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERα and ERβ). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR ≫ PR N GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERβ. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process.

Evidence of the effect of dehydration on physiological responses to hypoxia is limited. The purpose of this study was to determine the effect of hypohydration severity on physiological, renal hormonal and psychological responses to acute hypoxia. Eight males completed intermittent walking tests under normobaric hypoxic conditions (FI O 2 = 0.13) after completing four separate hypohydration protocols, causing change in body mass of approximately 0% (EU), -1% (H1), -2% (H2) and -3% (H3). Physiological and psychological markers were monitored throughout the 125 min test. Fluid controlling hormones were measured pre and post exposure. Heart rate, core temperature, peripheral arterial oxygen saturation (SpO 2 ), minute ventilation and urine osmolality were found to be significantly different between hydration conditions and correlated with Lake Louise Questionnaire score (LLQ) (P \ 0.05). LLQ score increased with hypohydration severity above H2 (EU 1.3 ± 1; H1 1.2 ± 1; H2 2.7 ± 2; H3 3.9 ± 2) (P \ 0.001). Antidiuretic hormone and aldosterone increased over the test, but were not different between hydration conditions (P \ 0.05). Atrial natriuretic peptide showed no change over time, or with conditions. Therefore, renal hormones are not influenced by hypohydration severity during moderate intensity hypoxic exercise. Hypohydration less than -2% induces greater physiological strain during hypoxic exercise and may cause rise in symptoms such as, fatigue, headache, nausea and lightheadedness.

Aldosterone exerts its best known sodium homeostasis actions by controlling sodium excretion at the level of the distal tubules via activation of the apical epithelial sodium channel and the basolateral Na(+)/K(+)ATPase pump. Recently, this mineralocorticoid hormone has been demonstrated to act on the heart and blood vessels. Excess release of aldosterone in relation to the salt status induces both genomic and nongenomic effects that by promoting endothelial dysfunction, and vascular and cardiorenal adverse remodeling, contribute to the target organ damage found in hypertension, heart failure, myocardial infarction, and chronic renal failure. Mineralocorticoid receptor blockers have been shown to be highly effective in resistant hypertension and to slow down heart failure progression, and in experimental animals, the development of atherosclerosis. Blockade of the action of aldosterone and potentially other mineralocorticoid steroids has been increasingly demonstrated to be an extre...

Observational studies indicate a significant relation between dietary sodium and level of blood pressure. However, the role of salt sensitivity in the development of resistant hypertension is unknown. The present study examined the effects of dietary salt restriction on office and 24-hour ambulatory blood pressure in subjects with resistant hypertension. Twelve subjects with resistant hypertension entered into a randomized crossover evaluation of low (50 mmol/24 hoursϫ7 days) and high sodium diets (250 mmol/24 hoursϫ7 days) separated by a 2-week washout period. Brain natriuretic peptide; plasma renin activity; 24-hour urinary aldosterone, sodium, and potassium; 24-hour ambulatory blood pressure monitoring; aortic pulse wave velocity; and augmentation index were compared between dietary treatment periods. At baseline, subjects were on an average of 3.4Ϯ0.5 antihypertensive medications with a mean office BP of 145.8Ϯ10.8/83.9Ϯ11.2 mm Hg. Mean urinary sodium excretion was 46.1Ϯ26.8 versus 252.2Ϯ64.6 mmol/24 hours during low-versus high-salt intake. Low-compared to high-salt diet decreased office systolic and diastolic blood pressure by 22.7 and 9.1 mm Hg, respectively. Plasma renin activity increased whereas brain natriuretic peptide and creatinine clearance decreased during low-salt intake, indicative of intravascular volume reduction. These results indicate that excessive dietary sodium ingestion contributes importantly to resistance to antihypertensive treatment. Strategies to substantially reduce dietary salt intake should be part of the overall treatment of resistant hypertension. (Hypertension. 2009;54:475-481.)

Rossier BC, Baker ME, Studer RA. Physiol Rev 95: 297– 340, 2015; doi:10.1152/physrev.00011.2014.
Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na+-K+-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na+-K+ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases.

Introduction: The renin-angiotensin-aldosterone-system (RAAS) is one of the most important systems involved in the pathogenesis of cardiovascular diseases. Its role in stress response has been generally neglected, although the progression of cardiovascular disease is considerably increased in the presence of stress and especially in the presence of depression risk.

Aims Both sediment and light are essential factors regulating the growth of submerged macrophytes, but the role of these two factors in regulating root morphology and physiology is far from clear. The responses of root morphology and physiology to sediment type and light availability in the submerged plant Myriophyllum spicatum were studied and the hypothesis was tested that a trade-off exists in root growth strategy between internal aeration and nutrient acquisition. † Methods Plants were grown on two types of sediment (fertile mud and an infertile mixture of mud and sandy loam) and under three levels of light availability (600, 80 and 20 m mol m 22 s 21 ) in a greenhouse. † Key Results The significantly higher alcohol dehydrogenase (ADH) activity in root tissues indicated that oxygen deficiency existed in the plants growing in fertile mud and low (or high) light environments. Significantly, low plant N and P concentrations indicated that nutrient deficiency existed in the mixed sediment and high light environment. As a response to anoxia, plants did not change the porosity of the main roots. The effect of sediment type on root morphology was insignificant under higher light environments, whereas root diameter generally decreased but specific root length (SRL) increased with decreasing light availability. Both low light and fertile mud jointly led to lack of second-order laterals. More biomass was allocated to lateral roots in infertile environments, whereas mass fractions of laterals were lower in low light and mud environments. † Conclusions These data indicate that this plant can achieve the trade-off between internal aeration and nutrient acquisition by adjusting the structure of the root system and the pattern of biomass allocation to different root orders rather than root morphology and root porosity.

Orexins-A and B are two novel hypothalamic peptides, which, like leptin and neuropeptide-Y (NPY), are involved in the central regulation of feeding. Since leptin and NPY were found to modulate adrenal function, we have examined whether orexins are able to directly aect rat adrenal steroid secretion. Both orexin-A and orexin-B raised basal corticosterone secretion of dispersed rat zona fasciculata±reticularis (ZF/R) cells, their maximal eective concentration being 10 À8 M. In contrast, orexins did not aect either maximally ACTH (10 À9 M)-stimulated corticosterone production by ZF/R cells or the basal and agonist-stimulated aldosterone secretion of dispersed zona glomerulosa cells. The ACTH-receptor antagonist corticotropininhibiting peptide (10 À6 M) annulled corticosterone response of ZF/R cells to ACTH (10 À9 M), but not to orexins (10 À8 M). Orexins (10 À8 M) enhanced cyclic-AMP release by ZF/R cells, and the selective inhibitor of protein-kinase A (PKA) H-89 (10 À5 M) abolished corticosterone responses to both ACTH (10 À9 M) and orexins (10 À8 M). A subcutaneous injection of both orexins (5 or 10 nmol/kg) evoked a clear-cut increase in the plasma concentration of corticosterone (but not aldosterone), the eect of orexin-A being signi®cantly more intense than that of orexin-B. Collectively, these ®ndings suggest that orexins exert a selective and direct glucocorticoid secretagogue action on the rat adrenals, acting through a receptor-mediated activation of the adenylate cyclase/PKA-dependent signaling pathway. #

Marine mammals are routinely caught in the wild in an effort to monitor their health. However, capture-associated stress could potentially bias various biochemical parameters used to monitor the health of these wild caught animals. Therefore, the effects of capture were quantified by measuring plasma adrenal steroids and arginine vasopressin (AVP) in free-ranging bottlenose dolphins (Tursiops truncatus) (n= 31). Total capture and restraint times were also correlated to hormone concentrations to quantify the effects of capture. Significant, positive correlations between corticosterone and cortisol (R= 0.752; P B0.0001), and between corticosterone and aldosterone (R = 0.441; P= 0.045) were demonstrated. Significant correlations between capture and restraint time and hormone levels were not observed. Animals restrained for less than 20 min exhibited hormone levels similar to those for animals restrained for more than 20 min. The positive correlations among the adrenal steroids suggest that release of these steroids was stimulated by adrenocorticotropin (ACTH). The lack of a correlation between cortisol and AVP indicates that AVP did not influence ACTH-induced cortisol release in this situation. The study suggests that (1) a typical hypothalamic-pituitary-adrenal axis is present in these animals, and (2) the relatively short capture and restraint times did not induce a significant neuroendocrine stress response.

Exposure to excess aldosterone results in cardiac damage in hypertensive states. We evaluated the long-term cardiac structural and functional evolution in patients with primary aldosteronism after surgical or medical treatment. Fifty-four patients with primary aldosteronism were enrolled in a prospective study and were followed for a mean of 6.4 years after treatment with adrenalectomy (nϭ24) or spironolactone (nϭ30). At baseline, echocardiographic measurements of patients with primary aldosteronism were compared with those of 274 patients with essential hypertension. Patients with primary aldosteronism had greater left ventricular mass, more prevalent left ventricular hypertrophy, lower early:late-wave diastolic filling velocities ratio, and longer deceleration time than patients with essential hypertension but no differences in relative wall thickness and systolic function. During follow-up, average blood pressure was 135/82 and 137/82 mm Hg in patients treated with adrenalectomy and spironolactone, respectively. In the initial 1-year period, left ventricular mass decreased significantly only in adrenalectomized patients. Subsequent changes in left ventricular mass were greater in patients treated with spironolactone, with an overall change from baseline to the end of follow-up that was comparable in the 2 groups. Prevalence of hypertrophy decreased in both treatment groups, whereas diastolic parameters had only mild and nonsignificant improvement. Changes in blood pressure and pretreatment plasma aldosterone were independent predictors of left ventricular mass decrease in both treatment groups. Thus, in the long-term, both adrenalectomy and spironolactone are effective in reducing left ventricular mass in patients with primary aldosteronism, with effects that are partially independent of blood pressure changes. (Hypertension. 2007;50:911-918.) Key Words: adrenalectomy Ⅲ echocardiography Ⅲ left ventricular hypertrophy Ⅲ spironolactone Ⅲ diastolic filling F or many decades, aldosterone has been seen as a hormone almost exclusively involved in the regulation of body fluids, maintenance of electrolyte balance, and blood pressure homeostasis. 1 More recent views, however, indicate that aldosterone can contribute to cardiac damage independent of blood pressure. 2 In animal studies, exposure to excess aldosterone levels has been associated with collagen deposition, myocardial fibrosis, and ventricular remodeling, 3 and 2 large clinical trials have reported a significant decrease in the mortality rate of patients with heart failure who were treated with aldosterone antagonists. Primary aldosteronism is a disease associated with hypertension that offers an important clinical opportunity for assessing the effects of excess aldosterone on the cardiovascular system because, in this condition, its effects are isolated from those of the renin-angiotensin axis. The widespread use of the aldosterone:renin ratio as a screening test has led to more efficient identification of this endocrine disorder. Cardiac structural and functional changes are common consequences of hypertensive states and have been demonstrated also in patients with primary aldosteronism, along with some additional surrogate cardiovascular end points (reviewed in Reference 2). Many cross-sectional echocardiographic evaluations and a few short-term follow-up studies have reported variable results, 8 -20 with excess left ventricular (LV) hypertrophy and diastolic dysfunction being the most common, 8 -15 although not uniformly detected, 16 -20 abnormalities. We have further explored the relationship between aldosterone and the heart by assessing, in the long term, cardiac anatomic and functional evolution of patients with primary aldosteronism after treatment with adrenalectomy or aldosterone antagonists.

Exposure to chemicals commonly occurs in the form of mixtures. Methods and models are required to analyze and predict the effect of mixtures in order to improve risk assessment. The steroidogenesis and hormone production of the adrenal gland is a sensitive target for endocrine-disrupting chemicals including imidazoles. Here, we exposed human adrenocortical H295R cells to the individual imidazole fungicides prochloraz, ketoconazole, imazalil and their mixtures and analyzed the effects on secretion of cortisol and aldosterone and the effects on steroidogenic gene expression.