Age-Related Changes in Concentric and Eccentric Isokinetic Peak Torque of the Trunk Muscles in Healthy Older Versus Younger Men.

This study investigated age-related changes in trunk muscle function in healthy men and the moderating effect of physical activity. Twelve older (67.3 ± 6.0 years) and 12 younger (24.7 ± 3.1 years) men performed isokinetic trunk flexion and extension tests across a range of angular velocities (15°/s-180°/s) and contractile modes (concentric and eccentric). For concentric trunk extension, mixed-effects analysis of covariance revealed a significant interaction between Angular velocity × Age group (p = .026) controlling for physical activity. Follow-up univariate analysis of covariance revealed that the younger group produced significantly greater peak torque for all concentric extension conditions. Eccentric trunk strength was somewhat preserved in the older group. Age-related changes in trunk strength were independent of physical activity. The normal loss of trunk muscle strength in older age is muscle- and contractile-mode specific. These findings provide guidance for effective intervention strategies to offset adverse health outcomes related to trunk strength loss in older adults.

Cardiopulmonary and metabolic physiology during hemodialysis and inter/intradialytic exercise.

Hemodialysis is associated with numerous symptoms and side effects that, in part, may be due to subclinical hypoxia. However, acute cardiopulmonary and metabolic physiology during hemodialysis is not well defined. Intradialytic and interdialytic exercise appear to be beneficial and may alleviate these side effects. To better understand these potential benefits, the acute physiological response to exercise should be evaluated. The aim of this study was to compare and characterize the acute physiological response during hemodialysis, intradialytic exercise, and interdialytic exercise. Cardiopulmonary physiology was evaluated during three conditions: 1) hemodialysis without exercise (HD), 2) intradialytic exercise (IDEx), and 3) interdialytic exercise (Ex). Exercise consisted of 30-min constant load cycle ergometry at 90% V̇O2AT (anaerobic threshold). Central hemodynamics (via noninvasive bioreactance) and ventilatory gas exchange were recorded during each experimental condition. Twenty participants (59 ± 12 yr, 16/20 male) completed the protocol. Cardiac output (Δ = -0.7 L/min), O2 uptake (Δ = -1.4 mL/kg/min), and arterial-venous O2 difference (Δ = -2.0 mL/O2/100 mL) decreased significantly during HD. Respiratory exchange ratio exceeded 1.0 throughout HD and IDEx. Minute ventilation was lower (P = 0.001) during IDEx (16.5 ± 1.1 L/min) compared with Ex (19.8 ± 1.0 L/min). Arterial-venous O2 difference was partially restored further to IDEx (4.6 ± 1.9 mL/O2/100 mL) compared with HD (3.5 ± 1.2 mL/O2/100 mL). Hemodialysis altered cardiopulmonary and metabolic physiology, suggestive of hypoxia. This dysregulated physiology contributed to a greater physiological demand during intradialytic exercise compared with interdialytic exercise. Despite this, intradialytic exercise partly normalized cardiopulmonary physiology during treatment, which may translate to a reduction in the symptoms and side effects of hemodialysis.NEW & NOTEWORTHY This study is the first, to our knowledge, to directly compare cardiopulmonary and metabolic physiology during hemodialysis, intradialytic exercise, and interdialytic exercise. Hemodialysis was associated with increased respiratory exchange ratio, blunted minute ventilation, and impaired O2 uptake and extraction. We also identified a reduced ventilatory response during intradialytic exercise compared with interdialytic exercise. Impaired arterial-venous O2 difference during hemodialysis was partly restored by intradialytic exercise. Despite dysregulated cardiopulmonary and metabolic physiology during hemodialysis, intradialytic exercise was well tolerated.

Ventilatory and chronotropic incompetence during incremental and constant load exercise in end-stage renal disease: a comparative physiology study.

Maximal O2 uptake is impaired in end-stage renal disease (ESRD), reducing quality of life and longevity. While determinants of maximal exercise intolerance are well defined, little is known of limitation during submaximal constant load exercise. By comparing individuals with ESRD and healthy controls, the aim of this exploratory study was to characterize mechanisms of exercise intolerance in participants with ESRD by assessing cardiopulmonary physiology at rest and during exercise. Resting spirometry and echocardiography were performed in 20 dialysis-dependent participants with ESRD (age: 59 ± 12 yr, 14 men and 6 women) and 20 healthy age- and sex-matched controls. Exercise tolerance was assessed with ventilatory gas exchange and central hemodynamics during a maximal cardiopulmonary exercise test and 30 min of submaximal constant load exercise. Left ventricular mass (292 ± 102 vs. 185 ± 83 g, P = 0.01) and filling pressure (E/e': 6.48 ± 3.57 vs. 12.09 ± 6.50 m/s, P = 0.02) were higher in participants with ESRD; forced vital capacity (3.44 ± 1 vs. 4.29 ± 0.95 L/min, P = 0.03) and peak O2 uptake (13.3 ± 2.7 vs. 24.6 ± 7.3 mL·kg-1·min-1, P < 0.001) were lower. During constant load exercise, the relative increase in the arterial-venous O2 difference (13 ± 18% vs. 74 ± 18%) and heart rate (32 ± 18 vs. 75 ± 29%) were less in participants with ESRD despite exercise being performed at a higher percentage of maximum minute ventilation (48 ± 3% vs. 39 ± 3%) and heart rate (82 ± 2 vs. 64 ± 2%). Ventilatory and chronotropic incompetence contribute to exercise intolerance in individuals with ESRD. Both are potential targets for medical and lifestyle interventions.

Age-related degeneration of the lumbar paravertebral muscles: Systematic review and three-level meta-regression.

BACKGROUND: Morphological changes of the lumbar spine muscles are not well characterised with ageing. To further the understanding of age-related degeneration of the lumbar spine musculature, normative morphological changes that occur within the paravertebral muscles must first be established. METHODS: A systematic review and meta-regressions were conducted adhering to PRISMA guidelines. Searches for published and unpublished data were completed in June 2019. RESULTS: Searches returned 4781 articles. 34 articles were included in the quantitative analysis. Three-level meta-analyses showed age-related atrophy (r = -0.26; 95% CI: -0.33, -0.17) and fat infiltration (r = 0.39; 95% CI: 0.28, 0.50) in the lumbar paravertebral muscles. Degenerative changes were muscle-specific and men (r = -0.32; 95% CI: -0.61, 0.01) exhibited significantly greater muscle atrophy than women (r = -0.24; 95% CI: -0.47, 0.03). Imaging modality, specifically ultrasound, also influenced age-related muscle atrophy. Measurements taken across all lumbar levels revealed the greatest fat infiltration with ageing (r = 0.58, 95% CI: 0.35, 0.74). Moderators explained a large proportion of between-study variance in true effects for muscle atrophy (72.6%) and fat infiltration (79.8%) models. CONCLUSIONS: Lumbar paravertebral muscles undergo age-related degeneration in healthy adults with muscle, lumbar level and sex-specific responses. Future studies should use high-resolution imaging modalities to quantify muscle atrophy and fat infiltration.

Risk assessment of coccidostatics during feed cross-contamination: animal and human health aspects.

Coccidiosis, an intestinal plasmodium infection, is a major infectious disease in poultry and rabbits. Eleven different coccidiostats are licensed in the EU for the prevention of coccidiosis in these animal species. According to their chemical nature and main biological activity, these compounds can be grouped as ionophoric (monensin, lasalocid sodium, salinomycin, narasin, maduramicin and semduramicin) or non-ionophoric (robenidine, decoquinate, nicarbazin, diclazuril, and halofuginone) substances. Coccidiostats are used as feed additives, mixed upon request into the compounded feed. During the technical process of commercial feed production, cross-contamination of feed batches can result in the exposure of non-target animals and induce adverse health effects in these animals due to a specific sensitivity of mammalian species as compared to poultry. Residue formation in edible tissues of non-target species may result in unexpected human exposure through the consumption of animal products. This review presents recent risk assessments performed by the Scientific Panel on Contaminants in the Food Chain (CONTAM) of the European Food Safety Authority (EFSA). The health risk to non-target species that would result from the consumption of cross-contaminated feed with coccidostats at levels of 2, 5 or 10% was found to be negligible for most animal species with the exception of salinomycin and monensin in horses because of the particular sensitivity for which toxicity may occur when cross-contamination exceeds 2% and 5% respectively. Kinetic data and tissue analyses showed that residues of coccidiostats may occur in the liver and eggs in some cases. However, the level of residues of each coccidiostat in edible animal tissues remained sufficiently low that the aggregate exposure of consumers would not exceed the established acceptable daily intake (ADI) of each coccidiostat. It could be concluded that technical cross-contamination of animal feeds would not be expected to adversely affect the health of consumers.

The central role of myostatin in skeletal muscle and whole body homeostasis.

Myostatin is a powerful negative regulator of skeletal muscle mass in mammalian species. It plays a key role in skeletal muscle homeostasis and has now been well described since its discovery. Myostatin is capable of inducing muscle atrophy via its inhibition of myoblast proliferation, increasing ubiquitin-proteasomal activity and downregulating activity of the IGF-Akt pathway. These well-recognized effects are seen in multiple atrophy causing situations, including injury, diseases such as cachexia, disuse and space flight, demonstrating the importance of the myostatin signalling mechanism. Based on this central role, significant work has been pursued to inhibit myostatin's actions in vivo. Importantly, several new studies have uncovered roles for myostatin distinct from skeletal muscle size. Myostatin has been suggested to play a role in cardiomyocyte homeostasis, glucose metabolism and adipocyte proliferation, all of which are examined in detail below. Based on these effects, myostatin inhibition has potential to be widely utilized in many Western diseases such as chronic obstructive pulmonary disease, type II diabetes and obesity. However, if myostatin inhibitors are to successfully translate from bench-top to bedside in the near future, awareness must be raised on these non-traditional effects of myostatin away from skeletal muscle. Indeed, further research into these novel areas is required.

Melanocortin peptide therapy for the treatment of arthritic pathologies.

Arthritic pathologies are a major cause of morbidity within the western world, with rheumatoid arthritis affecting approximately 1% of adults. This review highlights the therapeutic potential of naturally occurring hormones and their peptides, in both arthritic models of disease and patients. The arthritides represent a group of closely related pathologies in which cytokines, joint destruction, and leukocytes play a causal role. Here we discuss the role of naturally occurring pro-opiomelanocortin (POMC)-derived melanocortin peptides (e.g., alpha melanocyte stimulating hormone [alpha-MSH]) and synthetic derivatives in these diseases. Melanocortins exhibit their biological efficacy by modulating proinflammatory cytokines and subsequent leukocyte extravasation. Their biological effects are mediated via seven transmembrane G-protein-coupled receptors, of which five have been cloned, identified, and termed MC1 to MC5. Adrenocorticotrophic hormone represents the parent molecule of the melanocortins; the first 13 amino acids of which (termed alpha-MSH) have been shown to be the most pharmacologically active region of the parent hormone. The melanocortin peptides have been shown to display potent anti-inflammatory effects in both animal models of disease and patients. The potential anti-inflammatory role for endogenous peptides in arthritic pathologies is in its infancy. The ability to inhibit leukocyte migration, release of cytokines, and induction of anti-inflammatory proteins appears to play an important role in affording protection in arthritic injury, and thus may lead to potential therapeutic targets.

Implementation of wireless power transfer and communications for an implantable ocular drug delivery system.

A wireless power transfer and communication system based on near-field inductive coupling has been designed and implemented. The feasibility of using such a system to remotely control drug release from an implantable drug delivery system is addressed. The architecture of the wireless system is described and the signal attenuation over distance in both water and phosphate buffered saline is studied. Additionally, the health risk due to exposure to radio frequency (RF) radiation is examined using a biological model. The experimental results demonstrate that the system can trigger the release of drug within 5 s, and that such short exposure to RF radiation does not produce any significant (

Development of a miniaturised drug delivery system with wireless power transfer and communication.

The development of an implantable system designed to deliver drug doses in a controlled manner over an extended time period is reported. Key performance parameters are the physical size, the power consumption and also the ability to perform wireless communications to enable the system to be externally controlled and interrogated. The system has been designed to facilitate wireless power transfer, which is very important for miniaturisation as it removes the need for a battery.

Intra-adrenal mechanisms in the response to chronic stress: investigation in a rat model of emotionality.

The exploratory behaviour of the genetically derived Maudsley rat model of emotionality has been well characterized. Maudsley reactives (MR) present with more 'anxious-like' behaviour than Maudsley nonreactives (MNR). Although this behaviour is assumed to be associated with altered adrenocortical function, the few studies addressing this issue have produced inconsistent findings. We therefore set out to investigate the adrenal endocrinology of the MR and MNR strains. Control Wistars, the ancestors of the Maudsleys, have been used for the first time to set the baseline for all the experiments carried out. It was found that the MNR strain had a significantly blunted adrenocorticotrophic hormone (ACTH) response to restraint stress compared with Wistars, but a normal corticosterone response. Conversely, the MR had a significantly exaggerated ACTH response to restraint stress, but a normal corticosterone response. This finding suggested that the MR adrenal is less sensitive to ACTH than the MNR. This was confirmed by investigating the corticosterone dose-response to ACTH in adrenals from the two strains incubated in vitro. Several possible intra-adrenal regulators were investigated, but the only significant molecular difference in the adrenal glands from the two strains was the level of expression of neuropeptide Y (NPY), which is known to be a stress-responsive peptide in the adrenal. We propose that intra-adrenal NPY is responsible for blunting adrenocortical responses to ACTH stimulation in the MR strain. The observed changes in adrenal NPY suggest that this rat strain may serve as a model of chronic stress, with the MR phenotype representing maladaptation.

Peptide YY: a potential therapy for obesity.

Obesity now represents a modern epidemic in western society with major health and economic consequences. Unfortunately, previous pharmacological approaches to the treatment of obesity have been associated with life-threatening side effects and limited efficacy. Over recent years there has been a marked increase in our understanding of the physiological mechanisms that regulate body weight and how these are perturbed in obesity. One therapeutic strategy is to develop drugs which both mimic and enhance the body's own satiety signals. The gut hormone peptide tyrosine tyrosine (PYY), which is released postprandially from the gastrointestinal tract, has recently been shown to be a physiological regulator of food intake. Peripheral administration of PYY reduces feeding in rodents via a mechanism which requires the Y2 receptor and is thought to primarily involve modulation of the hypothalamic arcuate nucleus (ARC) circuitry. In humans a single 90-minute infusion of PYY has been shown to markedly reduce subsequent 24-hour caloric intake in lean, normal-weight and obese subjects. Moreover, obese subjects have been found to have low levels of fasting and postprandial PYY suggesting a role for this hormone in the pathogenesis of obesity. Although studies examining the effects of chronic peripheral administration of PYY to humans are awaited, the results from continuous infusion studies in a number of obese rodent models are encouraging with reductions in food intake, body weight and adiposity observed. Potential therapeutic manipulations based on the PYY system include development of Y2 agonists, exogenously administration of PYY or increased endogenous release from the gastrointestinal tract.

Adrenal neuropeptides: regulation and interaction with ACTH and other adrenal regulators.

It is now well accepted that both the cortex and medulla of the mammalian adrenal gland receive a rich innervation. Many different transmitter substances have been identified in nerves supplying both cortex and medulla and, as well as catecholamines, a wide range of neuropeptides has been found in the adrenal gland. There have been several studies on the affects of age, sodium intake, stress, ACTH, and splanchnic nerve activity on the regulation of adrenal neuropeptide content. There is evidence that the abundance of each of these peptides is actively regulated. Although there have been many studies addressing the individual actions of various neurotransmitters on steroid secretion, adrenal blood flow, and adrenal growth, few have attempted to determine the nature of any interaction between neurotransmitters and the classical adrenal stimulants. There are, however, some significant interactions, particularly in the regulation of zona glomerulosa function. This review necessarily focuses on vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), as these are the most abundant transmitter peptides in the adrenal gland and the majority of studies have investigated their regulation and actions. However, substance P, calcitonin gene-related peptide (CGRP), neurotensin, and the enkephalins are included where appropriate. Finally, it has been suggested that certain neurotransmitters, particularly VIP, may interact with classical hormone receptors in the adrenal, notably the ACTH receptor. This review attempts to evaluate our current state of knowledge in each of these areas.

Minimizing risk using prediction uncertainty in neural network estimation fusion and its application to papermaking.

The paper presents Bayesian information fusion theory in the context of neural-network model combination. It shows how confidence measures can be combined with individual model estimates to minimize risk through the fusion process. The theory is illustrated through application to the real task of quality prediction in the papermaking industry. Prediction uncertainty estimates are calculated using approximate Bayesian learning. These are incorporated into model combination as confidence measures. Cost functions in the fusion center are used to control the influence of the confidence measures and improve the performance of the resultant committee.

Bacterial lipopolysaccharide directly stimulates cortisol secretion in human adrenal cells.

Adrenomedullin and pro-adrenomedullin N-terminal 20 peptide (PAMP) are expressed in vascular cells and in the adrenal cortex and medulla. Lipopolysaccharide (LPS), a bacterial product that induces septic shock, is a potent stimulant of adrenomedullin secretion in vascular cell types and is also known to stimulate the hypothalamo-pituitary-adrenal axis (HPA). The present study was designed to investigate the actions of LPS on the human adrenocortical cell line, H295R. Exposure of cells to LPS for 24 hours had no effect on adrenomedullin or PAMP secretion, but was found to significantly and selectively increase cortisol secretion with no effect on aldosterone. Dibutyryl cAMP, however, caused a significant increase in both adrenomedullin and PAMP release over this time period. There are two conclusions which can be drawn from these observations. First that adrenomedullin and PAMP are regulated by different mechanisms in vascular and adrenal cells and second, that LPS is able to directly stimulate cortisol secretion, with implications for the physiological response to septic shock.

Regulation of rat adrenal vasoactive intestinal peptide content: effects of adrenocorticotropic hormone treatment and changes in dietary sodium intake.

Vasoactive intestinal peptide (VIP) is well established as a paracrine regulator of adrenal function. It is present in nerves supplying the adrenal cortex, although previous studies have found that the amount of VIP in the outer zones of the rat adrenal is not affected by ligating the splanchnic nerve supplying the adrenal gland. The present studies were designed to investigate the mechanisms involved in regulating the VIP content of the rat adrenal gland. This study examined the effects of changes in electrolyte balance and adrenocorticotropic hormone (ACTH) administration on the adrenal content of VIP as measured by radioimmunoassay. Rats on a low sodium diet had a significantly increased capsular/zona glomerulosa immunoreactive VIP (irVIP) level, while rats on a high sodium diet had suppressed levels relative to controls. Changes in dietary sodium did not affect inner zone/medullary VIP content. Administration of ACTH caused a decrease in irVIP levels in the capsular/zona glomerulosa portion of the adrenal gland but had no effect on the inner zone/medulla. Analysis of mRNA encoding VIP revealed a large increase in expression of VIP in the sodium-deplete group compared with the control, with no change in VIP expression in the sodium-loaded group. ACTH treatment was found to significantly decrease VIP mRNA levels in the capsular portion. Neither ACTH treatment nor changes in sodium intake affected inner zones/medullary VIP message. These data suggest that VIP in the capsule and zona glomerulosa region of the adrenal cortex is regulated in response to the physiological status of the animal, with changes in capsular/zona glomerulosa VIP correlating with changes in zona glomerulosa function.

Neuropeptide Y and the adrenal gland: a review.

This paper sets out to review several aspects of NPY and adrenal function, starting with the localisation of NPY in the adrenal, then describing the regulation of NPY release and considering whether the adrenal is a significant source of circulating NPY. The review then describes the regulation of adrenal content of peptide, and finally covers the actions of NPY on the adrenal gland, and the receptor subtypes thought to mediate these effects. The regulation and actions of NPY are discussed with reference to both the adrenal cortex and the medulla.

Adrenomedullin and calcitonin gene-related peptide receptors in the rat adrenal cortex.

The actions of calcitonin gene-related peptide (CGRP) and adrenomedullin on steroid hormone secretion from the rat zona glomerulosa are controversial, with reports in the literature of both stimulatory and inhibitory effects. It appears that these results previously obtained may depend on the nature of the receptors expressed by zona glomerulosa cells. The present study was designed to characterize CGRP and adrenomedullin binding in the rat adrenal zona glomerulosa. Specific binding for both peptides was observed, with two CGRP receptor sites found, and a single population of adrenomedullin receptors, but approximately twice the number of adrenomedullin binding sites. Messenger RNA analysis of the candidate genes for CGRP and adrenomedullin receptors revealed an abundance of both CRLR and RAMP1 mRNA, suggesting that these genes encode one of the CGRP receptors in this tissue. Much less RAMP2 expression was observed, however, which suggests that another gene product may account for adrenomedullin binding. There were very low levels of RAMP3 expression, but abundant L1 mRNA present, which may suggest that this rather controversial receptor has a role in the adrenal. The finding of distinct and specific adrenomedullin and CGRP binding in this tissue may account for the different effects these peptides appear to exert on adrenal function.

Substance P is involved in terminating the hypothalamo- pituitary-adrenal axis response to acute stress through centrally located neurokinin-1 receptors.

The neurokinin substance P (SP) has been previously shown to inhibit basal hypothalamo-pituitary-adrenal (HPA) axis activity. This study was designed to investigate the effects of central injection of the specific neurokinin-1 receptor antagonist RP67580 on the HPA axis response to acute restraint stress. In non-restrained rats injected with RP67580, plasma ACTH and corticosterone levels were elevated at 30 and 60 min compared to rats injected with vehicle, but there were no differences between vehicle and RP67580 groups at 4h. In restrained rats injected with vehicle, plasma ACTH and corticosterone levels were significantly elevated at 30 min and 60 min following initiation of the stress but had returned to basal levels at 4h. In restrained rats injected icv with RP67580, plasma corticosterone and ACTH levels were significantly elevated at 30 min and 60 min, with no significant differences compared to the restraint stressed vehicle-injected group. However, in the RP67580-injected group, corticosterone and ACTH levels remained significantly elevated at 4h following onset of restraint compared to those in the restraint stressed vehicle-injected group. Corticotrophin-releasing factor mRNA levels in the parvocellular subdivision of the paraventricular nucleus of the hypothalamus and POMC mRNA levels in the anterior pituitary were significantly increased in the stressed group 4h following injection with RP67580 compared to the stressed group injected with vehicle alone. These data show that endogenous SP does not inhibit the initial magnitude of the HPA axis response to restraint stress, but does act through neurokinin-1 receptors at a central level to reduce the duration of the response to stress. This suggests that SP may be an important central agent controlling the transition between acute and chronic stress.

Adrenomedullin receptor is found exclusively in noradrenaline-secreting cells of the rat adrenal medulla.

Adrenomedullin, originally identified in the adrenal medulla, has binding sites in the adrenal gland; however, its role in the adrenal medulla is unclear. This study was designed to characterise adrenomedullin binding sites in the rat adrenal medulla, using ligand binding studies, immunocytochemistry, and mRNA analysis. A single population of specific adrenomedullin receptors was identified in adrenal medullary homogenates. 125I-Adrenomedullin was displaced only by adrenomedullin1-50 and not by calcitonin gene-related peptide or amylin at concentrations up to 100 nmol/L. The receptor K(D) was 3.64 nmol/L with a receptor density of 570 fmol/mg of protein. Analysis of mRNA revealed that the genes encoding both the putative adrenomedullin receptors, termed calcitonin receptor-like receptor (CRLR) and L1, were expressed in the rat adrenal medulla. Dual-colour indirect-labelled immunofluorescence was used to localise phenylethanolamine N-methyltransferase (PNMT) and the adrenomedullin receptor in the same section. PNMT is the enzyme that converts noradrenaline to adrenaline and is not expressed in noradrenaline-secreting cells. These studies revealed that both CRLR and L1 were expressed only in cells that did not express PNMT, suggesting that adrenomedullin receptors are only found in noradrenaline-secreting cells. Further evidence to support this conclusion was provided by the demonstration of colocalisation of adrenomedullin receptors with dopamine beta-hydroxylase, confirming the presence of the receptors in medullary chromaffin cells. Taken together, these data suggest that adrenomedullin acts through a specific adrenomedullin receptor in the rat adrenal medulla. RT-PCR and northern blot analysis revealed greater abundance of mRNA for L1 than for CRLR, possibly suggesting that L1 may be the major adrenomedullin receptor expressed in this tissue. As it has been reported that adrenomedullin is synthesised predominantly by adrenaline-secreting cells, it appears likely that adrenomedullin is a paracrine regulator in the adrenal medulla.

Actions of neuropeptide Y on the rat adrenal cortex.

Although several studies have demonstrated the presence of neuropeptide Y (NPY) in nerves supplying the mammalian adrenal cortex, its function in this tissue remains unclear, with reports of both stimulatory and inhibitory effects on aldosterone secretion apparently depending on the tissue preparation used. In the present study the effects of NPY on rat adrenal capsular tissue were investigated. NPY significantly stimulated aldosterone secretion in a dose-dependent manner, and this effect was abolished by atenolol, a beta1-adrenergic antagonist. NPY also stimulated the release of catecholamines from intact rat adrenal capsular tissue with the same dose-dependent relationship as the stimulation of aldosterone release. These observations suggest that the actions of NPY may be mediated by the local release of catecholamines from chromaffin cells within adrenal capsular tissue, as we have previously described for vasoactive intestinal peptide. The second part of this study concerned the NPY receptor subtype mediating the actions of NPY on the adrenal cortex. It was found that peptide YY stimulated aldosterone release with a comparable potency to NPY, whereas pancreatic polypeptide (PP) was without effect. The Y1 selective NPY analog Leu31Pro34NPY had a greater effect on aldosterone release than the Y2 selective analog NPY18-36. Studies using the specific Y1 receptor antagonist BIBP 3226 showed significant attenuation of the aldosterone response to NPY, but no effect on the response to added norepinephrine. Binding studies carried out using [125I]NPY revealed the presence of a single population of NPY-binding sites with a Kd of 12.25 nmol/liter and a binding capacity of 623 fmol/mg protein. Competition studies revealed displacement of [125I]NPY specific binding by NPY, peptide YY, and Leu31Pro34NPY, but not by other peptides. Messenger RNA analysis revealed the presence of messenger RNA coding for both the Y1 receptor and the Y4 receptor, but not the other subtypes. Taken together these data suggest that the effects of NPY on the rat adrenal cortex are mediated by the Y1 receptor subtype.