bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Compromised Intra‐Uterine Environment: Implications For Future Lung Health
Authors: Harding R , Cock ML , Louey S , Joyce BJ , Davey MG , Albuquerque CA , Hooper SB , Maritz GS 
Published: March 2003

SUMMARY1. Epidemiological studies of infants, children and adults indicate that prenatal compromises that restrict fetal growth and cause low birthweight increase the risk of respiratory deficiencies after birth.2. It is apparent that the lung has a limited ability to recover from early developmental compromises and that altered development can permanently impair lung architecture.3. Lung development in utero can be adversely affected by factors associated with fetal growth restriction, namely fetal hypoxaemia, reduced substrate supply and hypercortisolaemia.4. We have conducted a series of studies of respiratory development in chronically catheterized ovine fetuses and postnatal lambs in which growth restriction was induced during late gestation by embolizing the umbilico–placental vascular bed, a technique that replicates key aspects of human placental insufficiency.5. During late gestation, restricting the growth of the ovine fetus did not alter lung weight or lung liquid secretion or volume when each factor was related to bodyweight, but it did lead to increased lung DNA concentrations and an increased thickness of the air–blood barrier. Expression of pulmonary surfactant proteins A, B and C were not altered and, hence, it was unlikely that surfactant protein synthesis had been impaired by growth restriction.6. When growth restriction continued to term, lambs were born with a low birthweight and remained small compared with controls for 8 weeks after birth. Low‐birthweight lambs were mildy hypoxaemic and compliances of their lungs and chest wall were, respectively, decreased and increased relative to controls. Pulmonary surfactant proteins A, B and C were not deficient, indicating that decreased lung compliance most likely had a structural basis.7. Morphometric analysis of lungs at 8 weeks after birth indicated that low‐birthweight lambs had increased alveolar wall thicknesses, less ‘air‐space’ and thicker blood–air barriers. These properties would be expected to restrict pulmonary gas exchange and decrease pulmonary compliance.8. We conclude that growth restriction during early development can have lasting adverse effects on the lungs and chest wall and that these may be sufficient to affect respiratory function throughout later life as well as advancing ageing of the lungs.
Experimental Biology 2000 Symposium on Differential Control of Sympathetic Outflow DIFFERENTIAL PATTERNS OF SYMPATHETIC RESPONSES TO SELECTIVE STIMULATION OF NUCLEUS TRACTUS SOLITARIUS PURINERGIC RECEPTOR SUBTYPES
Authors: Scislo Tadeusz J , Kitchen Amy M , Augustyniak Robert A , O'Leary Donal S 
Published: March 2003

SUMMARY1. Studies are described that indicate that stimulation of different purinergic receptor subtypes (A1, A2A and P2X) located in the sub‐postremal nucleus tractus solitarius (NTS) evokes qualitatively and quantitatively different regional haemodynamic and efferent sympathetic responses.2. Stimulation of A2A receptors evoked the most diverse pattern of regional sympathetic responses: preganglionic adrenal nerve activity (pre‐ASNA) was increased, lumbar sympathetic nerve activity (LSNA) did not change, while renal (RSNA) and post‐ganglionic adrenal (post‐ASNA) sympathetic nerve activity was decreased. Stimulation of A1 receptors evoked qualitatively uniform, although quantitatively different, sympathoactivation: ↑pre‐ASNA > ↑RSNA >↑LSNA. Stimulation of P2X receptors evoked qualitatively uniform, although quantitatively different, sympathoinhibition: ↓RSNA = ↓post‐ASNA > ↓LSNA = ↓pre‐ASNA.3. These qualitatively and quantitatively different patterns of regional sympathetic responses strongly suggest that purinergic receptor subtypes may be specifically located and differentially expressed on NTS neurons/neural terminals that control different sympathetic outputs. Different NTS purinoceptors may contribute to patterned autonomic responses observed in specific physiological or pathological situations.
Proceedings of the Australian Physiological and Pharmacological Society Symposium: The Hypothalamus DISTRIBUTION, REGULATION AND ROLE OF HYPOTHALAMIC GALANIN SYSTEMS: RENEWED INTEREST IN A PLEIOTROPIC PEPTIDE FAMILY
Authors: Gundlach Andrew L , Burazin Tanya Cd , Larm Jari A 
Published: March 2003

SUMMARY1. Galanin peptide and galanin receptor‐binding sites are known to be widely distributed within the central nervous system, particularly in the hypothalamus in the preoptic area, the paraventricular (PVN) and supraoptic (SON) nuclei and the arcuate nucleus/median eminence.2. The present brief review focuses on some recent studies of the regional and cellular localization of mRNA encoding galanin and two galanin receptor subtypes (GalR1 and GalR2) in the hypothalamus, regulation of galanin and/or galanin receptor expression in various nuclei by physiological stimuli, electrophysiological effects of galanin on hypothalamic neurons and the isolation and cloning of galanin‐like peptide (GALP), a putative endogenous ligand for GalR2.3. In situ hybridization studies in rat brain have demonstrated an abundance of GalR1 mRNA in SON, magnocellular (m) and parvocellular (p) PVN and dorsomedial, ventromedial and arcuate nuclei. In contrast, GalR2 mRNA is enriched in pPVN, but not mPVN, and is not detected in SON. In addition, GalR2 mRNA is present in the dorsomedial nucleus and is enriched in the arcuate nucleus compared with GalR1 transcripts, with numerous labelled cells in all subdivisions.4. Neurons of the SON and PVN contain vasopressin and/or oxytocin, along with several other peptides, and the production and release of these hormones and peptides are modulated by various physiological stimuli. In relation to galanin systems, GalR1 and galanin expression is increased in magnocellular neurons by salt loading and is downregulated by lactation, consistent with an increased inhibition by galanin of vasopressin release following osmotic stimulation and a decreased inhibition of oxytocin release during lactation.5. Powerful inhibitory effects of galanin on the electrical (and secretory) activity of magnocellular neurons and complex presynaptic actions of galanin on the synaptic release of glutamate in the arcuate nucleus in vitro suggest an active role for multiple galanin receptor subtypes in the regulation of these hypothalamic systems in vivo.6. The recent isolation of a peptide from porcine hypothalamus (GALP‐1–60) that is structurally related to galanin and appears to be selective for GalR2 over GalR1 and the subsequent cloning of GALP cDNA from pig, rat and humans should allow studies to help reveal the physiological role played by galanin receptor subtypes (especially GalR2) and their multiple ligands in the hypothalamus and other brain areas.
Changes In Endogenous Monoamines In Aged Rats
Authors: Lee Jj , Chang Ck , Liu Im , Chi Tc , Yu Hj , Cheng Jt 
Published: March 2003

SUMMARY1. It has been documented that ageing may alter endogenous neurotransmitters. However, these results are controversial. Thus, in the present study, cerebral cortex and plasma from male Wistar rats aged 8 weeks and 6, 12 or 24 months were used to investigate the changes in monoamines using electrochemical detection.2. A marked decrease in L‐dihydroxyphenylalanine (L‐DOPA) was observed in aged rats. Like the decrease in dopamine (DA), levels of 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindolacetic acid (5‐HIAA), the major metabolite of 5‐HT, in aged rats were decreased in the cerebral cortex and plasma. Plasma levels of noradrenaline and levels of adrenaline in the cerebral cortex were also decreased in aged rats. Moreover, levels of 3,4‐dihydroxyphenylacetic acid (DOPAC), a metabolite of DA, in the cerebral cortex and plasma were reduced by ageing. The level of homovanillic acid (HVA) in all samples was markedly increased with ageing.3. The ratio of DOPAC/DA and 5‐HIAA/5‐HT, being closely linked with the activity of monoamine oxidase, was increased in the cerebral cortex and plasma with ageing. The ratio of HVA/DOPAC, an index of the activity of catechol‐O‐methyltransferase, was also higher in the cerebral cortex and plasma of aged rats.4. These data suggest that ageing may alter endogenous monoamines in both the brain and peripheral tissues.
Role Of Calcitonin Gene‐Related Peptide In Ischaemic Preconditioning In Diabetic Rat Hearts
Authors: Lu Rong , Hu Chang‐Ping , Peng Jun , Deng Han‐Wu , Li Yuan‐Jian 
Published: March 2003

SUMMARY1. It has been suggested that calcitonin gene‐related peptide (CGRP) is involved in the protection provided by ischaemic preconditioning in rat hearts and that ischaemic preconditioning is absent in diabetic rat hearts.2. In the present study, we tested the relationship between sensory nerve function and ischaemic preconditioning in diabetic rats.3. In 4‐ and 8‐week diabetic rats and age‐matched non‐ diabetic controls, 30 min global ischaemia and 40 min reperfusion caused a significant decrease in cardiac function and a marked increase in creatine kinase (CK) release. Ischaemic preconditioning, by three cycles of 5 min ischaemia and 5 min reperfusion, improved the recovery of cardiac function and decreased CK release during reperfusion in 4‐week diabetic rat hearts. However, the cardioprotection afforded by ischaemic preconditioning was lost in 8‐week diabetic rat hearts. Pretreatment with CGRP for 5 min also significantly improved the recovery of cardiac function and decreased CK release in rats subjected to 4 or 8 weeks of diabetes.4. The content of CGRP in the coronary effluent during ischaemic preconditioning was significantly increased in 4‐week diabetic rat hearts (P < 0.05). However, only a slight increase in the release of CGRP was shown in 8‐week diabetic rat hearts (P > 0.05).5. In summary, the present results suggest that the protection afforded by ischaemic preconditioning is attenuated in diabetic rats and that the change may be related to the reduction in CGRP release in diabetic rat hearts.
John Ludbrook APPS Symposium Neural Mechanisms In The Cardiovascular Responses To Acute Central Hypovolaemia
Authors: Evans Roger G , Ventura Sabatino , Dampney Roger Al , Ludbrook John 
Published: March 2003

SUMMARY1. The haemodynamic response to acute central hypovolaemia consists of two phases. During phase I, arterial pressure is well maintained in the face of falling cardiac output (CO) by baroreceptor‐mediated reflex vasoconstriction and cardio‐acceleration. Phase II commences once CO has fallen to a critical level of 50–60% of its resting value, equivalent to loss of approximately 30% of blood volume.2. During phase II, sympathetic vasoconstrictor and cardiac drive fall abruptly and cardiac vagal drive increases. In humans, this response is invariably associated with fainting and has been termed vasovagal syncope.3. In both experimental animals and in humans, the responses to acute central hypovolaemia are greatly affected by anaesthetic agents, in that the compensatory responses during phase I (e.g. halothane) or their failure during phase II (e.g. alfentanil) are blunted or abolished.4. Therefore, our present knowledge of the neurochemical basis of the response to hypovolaemia depends chiefly on the results of experiments in conscious animals. Use of techniques for simulating haemorrhage has greatly enhanced this research effort, by allowing the effects of multiple treatments on the response to acute central hypovolaemia to be tested in the same animal.5. The results of such experiments indicate that phase II of the response to hypovolaemia is triggered, at least in part, by a signal from cardiac vagal afferents. There is also strong evidence that phase II depends on brainstem δ1‐opioid receptor and nitrergic mechanisms and can potentially be modulated by circulating or neuronally released adrenocorticotropic hormone, brainstem serotonergic pathways operating through 5‐HT1A receptors and opioids acting through μ‐ and κ‐opioid receptors in the brainstem.6. Phase II also appears to require input from supramedullary brain centres. Future studies should determine how these neurotransmitter systems interact and their precise neuroanatomical arrangements.
Organs/Systems Potentially Involved In One Model Of Programmed Hypertension In Sheep
Authors: Dodic Miodrag , Baird Rebecca , Hantzis Vicky , Koukoulas Irene , Moritz Karen , Peers Arianne , Wintour E Marelyn 
Published: March 2003

SUMMARY1. When pregnant ewes and their fetuses are exposed to the synthetic glucocorticoid dexamethasone for 2 days early in pregnancy (days 26–28; term 145–150 days), female offspring have increased blood pressure relative to a control group. In one series, this was shown to be due to increased cardiac output, concomitant with a reset mean arterial pressure/heart rate reflex. The first group of such animals had, by the age of 7 years, left ventricular hypertrophy and reduced cardiac functional capacity.2. The elevation in blood pressure is not maintained by any change in the peripheral renin–angiotensin system (RAS).3. There is, however, preliminary evidence that some aspects of local RAS (particularly in the kidney and brain) could have participated in the ‘programming’ event. The levels of mRNA for angiotensin II receptors (AT1, AT2) and angiotensinogen are increased in the kidney of such dexamethasone‐treated fetuses in late gestation (130 days), some 100 days after steroid treatment. Similar increases in AT1 mRNA in the medulla oblongata of the fetal brain and large increases of mRNA for angiotensinogen occur in the hypothalamus.4. These findings, together with evidence from the literature, suggest that both the kidney and parts of the brain are affected by events that also ‘program’ high blood pressure in the offspring of animals in which the intra‐uterine environment has been perturbed at some stage.
Fetal Origins of Adult Disease Fetal Origins Of Adult Disease?
Authors: Morley Ruth , Dwyer Terence 
Published: March 2003

SUMMARY1. Associations between lower birthweight and higher blood pressure, increased risk of type 2 diabetes and coronary heart disease (CHD) have been observed in a number of different populations worldwide.2. The reason for this is still debated. Some believe that the observed associations can be explained on the basis of differences in postnatal growth, socioeconomic confounding or genetic factors. Two published studies of birthweight and CHD, with information on later size, suggest that both gestational and postnatal exposures are important. Associations between birthweight and blood pressure, seen in cohorts of twins treated as individuals, have generally remained when data are analysed within twin pairs. Furthermore, similar associations are seen in studies of animals with relative genetic homogeneity kept in standard conditions. These findings suggest that neither socioeconomic nor genetic factors are wholly responsible for the observed associations.3. If then, there is an underlying causal association, two issues are of fundamental importance. First, is fetal growth (for which birthweight is a summary measure) involved in the causal pathway or is the causal factor a fetal exposure independently associated with fetal growth and increased risk of adult cardiovascular disease? The answer is important in terms of our understanding, the potential for intervention and estimation of the public health implications. Second, are the classic risk factors for CHD in the causal chain between fetal exposures or growth and adult CHD? Most prospective studies measure these factors, but their role as intermediates is unproven.4. Intervention studies are the best way to test causal hypotheses, but our level of understanding is insufficient to justify such studies in humans, so we rely on animal studies to formally test causal hypotheses. In the present paper, we discuss design and statistical issues in relation to animal studies. The challenge in this field is to devise ways to identify and test potential causal hypotheses in humans.
The Kallikrein–Kinin System In Humans
Authors: Campbell Duncan J 
Published: March 2003

SUMMARY1. Kinin peptides are implicated in many physiological and pathological processes, including the regulation of blood pressure and sodium homeostasis, inflammation and the cardioprotective effects of preconditioning. In humans, the plasma and tissue kallikrein–kinin systems (KKS) generate bradykinin and kallidin peptides, respectively.2. We established methodology for the measurement of bradykinin and kallidin peptides and their metabolites in order to study the function of the plasma and tissue KKS in humans.3. Bradykinin peptides were more abundant than kallidin peptides in blood and cardiac atrial tissue, whereas kallidin peptides were predominant in urine. The levels of kinin peptides in tissue were higher than in blood, confirming the primary tissue localization of the KKS.4. Angiotensin‐converting enzyme inhibition increased blood levels of bradykinin and kallidin peptides.5. Blood levels of kallidin peptides were suppressed in patients with severe cardiac failure, indicating that the activity of the tissue KKS is suppressed in this condition.6. Bradykinin peptide levels were increased in the urine of patients with interstitial cystitis, suggesting a role for these peptides in the pathogenesis and/or symptomatology of this condition.7. Cardiopulmonary bypass, a model of activation of the contact system, activated both the plasma and tissue KKS.8. Measurement of individual bradykinin and kallidin peptides and their metabolites gives important information about the operation of the plasma and tissue KKS and their role in physiology and disease states.
Is Primary Aldosteronism Underdiagnosed In Clinical Practice?
Authors: Fiquet‐Kempf Béatrice , Launay‐Mignot Pauline , Bobrie Guillaume , Plouin Pierre‐François 
Published: March 2003

SUMMARY1. Primary aldosteronism is a syndrome consisting of hypertension, suppressed renin activity or concentration and high aldosterone levels in plasma or urine. The main steps in diagnosis are the determination of renin and aldosterone levels, the demonstration of renin–aldosterone dissociation and discrimination between idiopathic hyperplasia and Conn’s adenoma, with only Conn’s adenoma amenable to surgery.2. Patients with resistant hypertension and/or hypokalaemia should be screened for primary aldosteronism with simple, redundant hormonal tests. The aldosterone to renin ratio is a logical initial screening test, a high ratio demonstrating renin–aldosterone dissociation. Criteria for a high ratio should be determined in each laboratory.3. In patients with documented primary aldosteronism, computed tomography scan and adrenal vein sampling help to distinguish between idiopathic hyperplasia and Conn’s adenoma.4. Patients with low renin hypertension, idiopathic hyperplasia and Conn’s adenoma have overlapping values for plasma concentrations of potassium, renin and aldosterone and the aldosterone to renin ratio. Because primary aldosteronism subtypes are quantitative diseases, the true prevalence of primary aldosteronism cannot be defined.5. The use of sensitive screening tests (e.g. aldosterone to renin ratio) gives a higher prevalence of diagnosed cases of primary aldosteronism, but not of surgically correctable forms. Therefore, there is no clinical evidence that primary aldosteronism is underdiagnosed.6. There is a need for tests to predict the postoperative blood pressure outcome of surgery in subjects with Conn’s adenoma.
MINERALOCORTICOIDS AND CARDIAC FIBROSIS: THE DECADE IN REVIEW
Authors: Funder John 
Published: March 2003

SUMMARY1. Over the past decade, aldosterone has been shown to have direct extra‐epithelial actions and substantial (patho)physiological roles in the cardiovascular system in the context of inappropriate salt status. In experimental studies on uninephrectomized rats given 0.9% NaCl solution to drink, these include blood pressure elevation via activation of circumventricular mineralocorticoid receptors in the central nervous system and production of pressure‐independent cardiac hypertrophy and fibrosis by a direct effect on the heart.2. In the Randomized Aldactone Evaluation Study (RALES) trial, patients with severe congestive heart failure (CHF) were continued on their current therapy (angiotensin‐converting enzyme inhibitor, diuretic etc.) and given either placebo or spironolactone at an average dose of 26 mg/day. Mineralocorticoid receptor inhibition was accompanied by a 30% improvement in mortality and 35% less hospitalization, striking confirmation of a pathophysiological role for aldosterone in CHF.3. Although the current basic and clinical studies are conflicting, there is evidence both for aldosterone synthesis by the failing human heart and for substantial cardiac metabolism of aldosterone. The extent to which this potential paracrine source for aldosterone may be involved in cardiac hypertrophy and cardiac fibrosis remains to be established.4. Belatedly, aldosterone‐induced proteins (e.g. serum and glucocorticoid‐regulated kinase (SGK)) have been identified in epithelial mineralocorticoid target tissue. Studies are currently in progress on the cellular and molecular mechanisms involved in the coronary vasculitis provoked early in the mineralocorticoid/salt model, which, in turn, appears to trigger the subsequent perivascular and interstitial fibrotic response.
Angiotensin At1Receptor Signalling Pathways In Neurons
Authors: Sumners Colin , Fleegal Melissa A , Zhu Mingyan 
Published: March 2003

SUMMARY1. The aim of the present article is to review the intracellular signal transduction pathways that are influenced by the peptide angiotensin (Ang) II, acting via its type 1 (AT1) receptor, in neurons.2. The AT1receptors couple to a wide variety of signalling pathways in peripheral tissues, such as kidney, heart and vascular smooth muscle. A similar diversity of signalling mechanisms exists for AT1receptors in neurons.3. We outline the known neuronal AT1receptor signalling pathways as they relate to function. Pathways that couple activation of AT1receptors to short‐term changes in neuronal membrane ionic currents and firing rate will be reviewed. These are different from the pathways that elicit longer‐term changes in enzyme activity and gene expression and, ultimately, increases in noradrenaline synthesis.4. Novel AT1receptor signalling pathways discovered through gene expression profiling and their potential functional significance have been discussed.