bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHANGES IN BLOOD AND RED CELL VOLUME IN THE NEONATAL LAMB AND THE EFFECT OF INSULIN‐LIKE GROWTH FACTOR I
Authors: Moritz Karen M. , Owens Phillip C. , Wintour E Marelyn 
Published: June 2007

SUMMARY1. Blood volume was measured weekly using [51Cr]‐labelled red cells in 10 lambs from 3 to 10 weeks of age. Red cell and plasma volumes were calculated using the measured blood volume and haematocrit. Other parameters, including plasma erythropoietin, urea, creatinine and glucose, were measured twice weekly. The results were compared to a group of five lambs that received an infusion of insulin‐like growth factor I (IGF‐I).2. In control lambs, plasma volume increased linearly by 47 ± 7 mL/week over the experimental period. Red cell volume only increased by 10 ± 2 mL/week during weeks 3–7, but then increased by 25 ± 2 mL/week over weeks 7–10. Haematocrit declined from 28.0 ± 1.6 to 24.7 ± 1.7% over weeks 3–7 and then increased to 30.7 ± 1.1% by week 10.3. In 10 control lambs infused for 8 days (starting at 22–26 days of age) with 10 mmol/L HCl, there was a decrease in plasma IGF‐I concentrations, 3 days after the start of infusion. In five lambs infused for 8 days with IGF‐I (6 μg/kg per h) plasma IGF‐I concentration was maintained significantly (P < 0.01) higher than that of the controls.4. There was no significant difference in haematocrit, red cell or plasma volumes between the treatment groups and no reticulocytosis was observed. Plasma erythropoietin concentrations did not change over the infusion period in either group.5. Serum urea decreased significantly in the IGF‐I infused group but serum creatinine did not change in either group during the infusion period. In both the groups, there was a significant decrease in glucose, urea and creatinine over weeks 3–10 after birth. There was no difference in growth rates between the two groups.6. Thus, it appears that the observed changes in haematocrit are due to a constant increase in plasma volume with varying rates of red cell volume increases.7. IGF‐I infused at a dose that maintains physiological concentrations and alters protein metabolism does not result in increased erythropoietin or erythropoiesis during the neonatal period of the lamb.
CNS PATHWAYS MEDIATING CARDIOVASCULAR REGULATION OF VASOPRESSIN
Authors: Renaud Leo P. 
Published: June 2007

SUMMARY1. The release of vasopressin from the neurohypophysial terminals of hypothalamic magnocellular neurosecretory neurons is subject to regulation by peripheral baroreceptors, cardiopulmonary volume receptors and circulating angiotensin II. Information from these sources is transmitted through different pathways to achieve different influences on the excitability of the vasopressin‐secreting cells.2. A brief increase in arterial pressure, sufficient to activate baroreceptors, is associated with a transient and selective GABAergic inhibition of these neurosecretory neurons, achieved through a multisynaptic pathway that involves ascending catecholaminergic fibres and neurons in the diagonal band of Broca. A decrease in arterial pressure activates peripheral low volume receptors and initiating neural inputs that result in an increase in the excitability of vasopressin‐secreting neurons, achieved via pathways that include direct projections from caudal ventrolateral medulla A1 neurons.3. Hypotension also releases renal renin and leads to the formation of angiotensin II; binding of this hormone to AT1 receptors on subfornical organ neurons promotes activation of a central angiotensinergic input that evokes a predominantly excitatory effect on vasopressin neurons.
ROLE OF THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS IN CARDIOVASCULAR REGULATION
Authors: Blair Martha L. , Piekut Diane , Want Andrew , Olschowka John A. 
Published: June 2007

SUMMARY1. The paraventricular hypothalamic nucleus (PVH) is a complex structure with both neuroendocrine and autonomic functions. It is a major source of vasopressin and the primary source of corticotropin‐releasing factor. In addition, parvicellular PVH neurons have reciprocal connections with brain‐stem autonomic centres and directly innervate sympathetic preganglionic neurons. Evidence is reviewed which indicates that in conscious rats PVH activation increases blood pressure, heart rate, renal nerve activity and plasma renin activity.2. In conscious rats, a non‐hypotensive haemorrhage (13 mL/kg blood loss over 24 min) results in increased numbers of Fos‐immunoreactive cell nuclei within both magnocellular and parvicellular PVH neurons, including the ventral medial parvicellular regions known to contain neuronal projections to brainstem autonomic centres and spinal cord sympathetic preganglionic neurons.3. Cell‐selective ibotenate lesions of the parvicellular PVH significantly blunt the corticosterone response but do not alter blood pressure, heart rate or plasma renin concentration response to non‐hypotensive or hypotensive haemorrhage. This and earlier studies indicate that, while the PVH is necessary for the corticosterone response and contributes to increased vasopressin release during blood loss, it does not play an important role in the sympathetic nervous system and renin‐angiotensin responses to hypovolaemia and hypotension.4. There is evidence to indicate that the parvicellular PVH serves as a necessary relay for cardiovascular and renin responses to certain behavioural stressors. We propose that cardiovascular information relayed to parvicellular PVH autonomic regions may be used to modulate behavioural, rather than homeostatic, effects on haemodynamics and renin release.
ROLE OF THE DORSOMEDIAL HYPOTHALAMUS IN THE CARDIOVASCULAR RESPONSE TO STRESS
Authors: DiMicco Joseph A. , Stotz‐Potter Elizabeth H. , Monroe Amy J. , Morin S Michelle 
Published: June 2007

SUMMARY1. Disinhibition of the dorsomedial hypothalamus (DMH) in rats by local microinjection of GABAA receptor antagonists evokes behavioural and physiological changes resembling those seen in acute experimental stress.2. Conversely, similar microinjection of muscimol, a potent agonist at inhibitory GABAA receptors, virtually abolishes stress‐induced increases in heart rate and arterial pressure.3. Blockade of excitatory amino acid (EAA) receptors in the DMH also attentuates stress‐induced cardiovascular changes and microinjection of kainate, AMPA or NMDA at low doses elicits cardiovascular effects resembling those seen in stress. Paradoxically, injection of higher doses of NMDA or of glutamate into this region has no consistent effect.4. The cardiovascular effects of bicuculline methiodide, a GABAA receptor antagonist, as well as those of NMDA and/or kainate were assessed after identical injection into either the DMH, the paraventricular nucleus (PVN) or the area between the two nuclei in both anaesthetized and conscious rats. For each agent, a similar pattern was seen, with the largest increases in heart rate and arterial pressure occurring after injection into the DMH and the smallest changes resulting from injection into the PVN.5. In a parallel study, bilateral microinjection of muscimol into the DMH dramatically reduced air stress‐induced cardiovascular changes; similar injection into the area of the PVN had no effect, while injection into the area between the nuclei produced an intermediate effect.6. Our findings suggest that activation of neurons in the region of the DMH mediates stress‐induced cardiovascular changes and that the activity of these neurons may be determined by the balance of tone at inhibitory GABAA receptors and EAA receptors.
FOREBRAIN PATHWAYS AND THEIR BEHAVIOURAL INTERACTIONS WITH NEUROENDOCRINE AND CARDIOVASCULAR FUNCTION IN THE RAT
Authors: Bohus Béla , Koolhaas Jaap M. , Korte S Mechiel , Roozendaal Benno , Wiersma Anja 
Published: June 2007

SUMMARY1. The forebrain is a major organizer of the complex behavioural, physiological and neuroendocrine responses to environmental challenges of a stressful nature.2. Combined physiological and neuroanatomical studies suggest that a specific forebrain‐brain stem network, composed of connections between the central nucleus of the amygdala, the paraventricular nucleus of the hypothalamus, the mesencephalic cuneiform nucleus, the parabrachial nucleus and the dorsal motor nucleus of the vagus nerve, may be important for integrating behavioural and physiological responses.3. Based on studies using bilateral electrolytic lesions of the central nucleus of the amygdala, it has become clear that the central nucleus of the amygdala is one of the key structures involved in unconditioned responses to inescapable footshock. These responses include freezing behaviour, tachycardia and the release of adrenaline, noradrenaline, prolactin and corticosterone. However, this nucleus is involved only in the freezing behaviour and bradycardiac responses to conditioned emotional stress or to social defeat.4. Both peptidergic (corticotropin releasing hormone and vasopressin/oxytocin) and aminergic (noradrenaline and dopamine) mechanisms in the central amygdala are involved in the regulation of integrated behavioural, physiological and neuroendocrine stress responses. This is indicated by studies with an infusion of an agonist and/or antagonist of the peptides or neurotransmitters into the central amygdala of freely moving rats. Sympathetic cardiac control is intensified by corticotropin releasing hormone and oxytocin, probably by inhibiting vagal output. In contrast, vagal activity is facilitated by vasopressin, noradrenaline and dopamine.
A PROPOSED MECHANISM FOR THE CARDIOPROTECTIVE EFFECT OF OESTROGEN IN WOMEN: ENHANCED ENDOTHELIAL NITRIC OXIDE RELEASE DECREASES CORONARY ARTERY REACTIVITY
Authors: Wellman George C. , Brayden Joseph E. , Nelson Mark T. 
Published: June 2007

SUMMARY1. During their reproductive years women have a much lower incidence of coronary heart disease than men of similar age. A cardioprotective effect of circulating oestrogen appears to be responsible for this decrease in cardiovascular mortality in women.2. Oestrogen can enhance nitric oxide (NO) production by the vacular endothelium, possibly through enhanced production of the enzyme NO synthase.3. Pressure‐induced constrictions in isolated coronary arteries from rats with physiological circulating levels of oestrogen are reduced compared to oestrogen‐deficient animals. This difference is abolished by endothelial removal or inhibition of NO synthase.4. NO through stimulation of guanylyl cyclase increases levels of the cytosolic second messenger cyclic GMP (cGMP) which activates a cGMP‐dependent protein kinase in vascular smooth muscle cells.5. Potassium currents through calcium‐activated channels in vascular smooth muscle cells are increased in response to NO or upon exposure to cGMP‐dependent protein kinase.6. In rat coronary arteries dilations to NO are reduced by agents which inhibit calcium‐activated potassium channels. NO can also hyperpolarize this tissue, suggesting membrane potential changes are involved in the response to NO.7. We propose that oestrogen increases NO production leading to more negative membrane potentials and decreased calcium entry in coronary vascular smooth muscle cells.
CORTICOSTEROIDS IN ESSENTIAL HYPERTENSION: MULTIPLE CANDIDATE LOCI AND PHENOTYPIC VARIATION
Authors: Connell JMC , Kenyon CJ , Ingram M. , Holloway C. , Jamieson A. , Panarelli M. , Inglis G. , Fraser R. 
Published: June 2007

SUMMARY1. The role of genetically determined changes in adrenal steroid production, metabolism and action in the pathogenesis of cardiovascular disease in man is considered by studying three loci that are important in corticosteroid function.2. Variation at the glucocorticoid receptor locus can be identified as a biallelic restriction fragment length polymorphism (Bcl1); subjects with contrasting genotypes show altered skin vasoconstrictor responses to topically applied budesonide without any significant change in leucocyte receptor binding characteristics.3. In a case control study of patients with essential hypertension, we have shown evidence of reduced 11β‐hydroxysteroid dehydrogenase activity, with an elevated ratio of cortisol to cortisone metabolites in urine.4. The genes encoding 11β‐hydroxylase and aldosterone synthase are highly homologous. Studies in the Milan hypertensive rat show variation at this locus, which may account for the increased steroid synthesis noted in the hypertensive strain; in man, a chimaeric gene comprising 5’ regulatory regions from 11β‐hydroxylase and 3’ coding sequence from aldosterone synthase accounts for the autosomal dominant condition Dexamethasone Suppressible Hyperaldosteronism. Variation in the precise location of the crossover site between the two genes does not account for the observed phenotypic heterogeneity in this condition.5. Measurement of basal plasma steroid levels in subjects with essential hypertension show an increased ratio of 11‐deoxycortisol/cortisol, consistent with reduced activity of 11β‐hydroxylase in the zona fasciculata.6. In summary, three loci involved in corticosteroid synthesis, metabolism and action can independently affect cardiovascular phenotypes; their roles in determining pathophysiological changes, including hypertension, remain to be studied.
ENDOTHELINS CONTRACT GUINEA‐PIG PULMONARY ARTERY AND ENHANCE ITS ADRENERGIC RESPONSE VIA ETA RECEPTORS
Authors: Matsuda H. , Kawaguchi A. , Uematsu M. , Ohmori F. , Nagata S. , Miyatake K. 
Published: June 2007

SUMMARY1. This study has pharmacologically characterized endothelin (ET) receptor subtype(s) mediating contraction and enhancement of adrenergic contraction in guinea‐pig pulmonary artery. Isometric tension of the isolated endothelium‐denuded ring preparations was measured in the presence of indomethacin (10−5 mol/L) and NG‐nitro‐L‐arginine methyl ester (l‐NAME; 3X10−4 mol/L) to exclude a mechanism via endothelium, cyclo‐oxygenase‐generated eicosanoids and nitric oxide.2. In the additional presence of tetrodotoxin (TTX; 3X10−7 mol/L), ET‐1 (10−11‐10−7 mol/L) concentration‐dependently contracted the preparations. The rank order of potency to contract the preparations among ET receptor agonists was ET‐1, sarafotoxin (STX) 6b>ET‐3>IRL 1620, STX 6c. BQ‐123 (7X10−7‐7X10−6 mol/L) concentration‐dependently shifted the concentration‐contraction curve for ET‐1 to the right in a parallel manner. Pretreatment with STX 6c (3X10−7 mol/L for 30 min) did not significantly desensitize contractions to ET‐1, ET‐3 or IRL 1620 (P>0.05; t‐test, 10 d. f.).3. ET‐1 (10−10‐10−9 mol/L) and STX 6b (10−9‐10−8 mol/L) significantly enhanced the electrical field stimulation‐induced contraction in a BQ‐123‐sensitive manner (P<0.05; t‐test, 24–38 d.f.), while ET‐3 (10−11‐10−8 mol/L) and STX 6c (10−11‐10−7 mol/L) did not affect contractions. ET‐1 (10−11 mol/L) significantly enhanced contractions to exogenous nor‐adrenaline in the presence of TTX (3X10−7 mol/L) (P<0.05; t‐test, 16 d.f.).4. These data indicate that the BQ‐123‐sensitive ETA receptor mediates both contraction and enhancement of adrenergic contractions in the guinea‐pig pulmonary artery.
INTERSTITIAL ADENOSINE AND FUNCTION IN RAT HEART IN VIVO: EFFECTS OF ADRENALINE AND 8‐CYCLOPENTYL‐1,3‐DIMETHYLXANTHINE
Authors: Headrick John P 
Published: June 2007

SUMMARY1. Left ventricular interstitial adenosine and cardiac function were studied in open chest rats during adrenaline stimulation and P1‐purinoceptor antagonism with 8‐cyclopentyl‐1,3‐dimethylxanthine (8‐CPT).2. Cardiac microdialysate adenosine concentration was 0.10±0.01 μmol/L (n= 24) under basal conditions, giving an estimated interstitial adenosine concentration of 0.27 μmol/L. Stimulation with 3.2 and 8.0 μg/kg per min adrenaline increased the rate‐pressure product (heart rate X systolic blood pressure) by 72 and 157%, respectively, and increased dialysate adenosine to 0.26±0.04 and 0.65±0.11 μmol/L (n= 12), respectively (interstitial concentrations of approximately 0.70 and 1.76 μmol/L).3. Treatment with 60 μg/kg per min 8‐CPT did not alter basal adenosine concentrations, but potentiated elevations in dialysate adenosine during infusion of 3.2 and 8.0 μg/kg per min adrenaline to 0.54±0.10 and 1.30±0.22 μmol/L, respectively (n= 12). Basal function and the response to 8.0 μg/kg per min adrenaline were unaltered by 8‐CPT, whereas elevations in heart rate and rate‐pressure product during stimulation with 3.2 μg/kg per min adrenaline were enhanced by 8‐CPT (by up to 30%).4. Studies in isolated hearts confirmed the inhibitory potency of 8‐CPT at A1vs A2 P1‐purinoceptors (e.g. pKB of 7.7±0.2 and 6.4±0.1 for 5′‐N‐ethyl carboxamidoadenosine‐mediated bradycardia and vasodilatation, respectively; n= 6). Studies in intact animals verified effective A1 blockade by 60 μg/kg per min 8‐CPT, but also revealed some inhibition of A2‐mediated responses.5. In conclusion, the data show that cardiac interstitial adenosine levels exist within a physiologically active range in vivo and increase dose‐dependently during graded adrenaline stimulation. Adenosine receptor antagonism enhances elevations in interstitial adenosine and modifies functional responses to moderate, but not high, doses of adrenaline. Whether 8‐CPT‐dependent elevations in interstitial adenosine are due to A1 inhibition vs inhibition of A2‐mediated vasodilatation requires further investigation.
NITRIC OXIDE INHIBITION IN AN OVINE MODEL OF HEART FAILURE
Authors: Rademaker Miriam Tessa , Fitzpatrick Michael Andrew , Richards Arthur Mark , Nicholls Michael Gary , Charles Christopher John , Frampton Christopher Miles , Ikram Hamid 
Published: June 2007

SUMMARY1. The role of nitric oxide (NO) in congestive heart failure was investigated by studying the acute haemodynamic, hormonal and renal effects of NG‐monomethyl‐l‐arginine (l‐NMMA), a nitric oxide inhibitor, given as incremental bolus doses in six sheep before (normal) and after induction of heart failure (HF) by rapid left ventricular pacing (LVP).2. l‐NMMA caused significant initial dose‐dependent rises in left ventricular systolic pressure, mean arterial pressure (MAP), peripheral resistance (PR) and left atrial pressure and declines in cardiac output in both normal and HF states (maximum response in 2–6 min). These responses were all but abolished when l‐arginine was given concurrently with l‐NMMA. The dose‐response curve for the l‐NMMA‐induced rise in MAP was shifted to the right following LVP (P<0.05), which is consistent with previous observations of blunted NO synthase activity in HF. A subsequent decline in MAP and PR to below prebolus levels was observed 30–60 min after l‐NMMA administration in the paced state. No significant hormonal or renal effects were observed.3. In conclusion, the present study confirms the important haemodynamic role played by endogenous NO in the normal state and demonstrates a blunted pressor response to NO inhibition in this model of heart failure.
STRUCTURE‐ACTIVITY RELATIONSHIPS FOR 4‐ANILINOQUINAZOLINES AS POTENT INHIBITORS AT THE ATP BINDING SITE OF THE EPIDERMAL GROWTH FACTOR RECEPTOR IN VITRO
Authors: Denny William A , Rewcastle Gordon W , Bridges Alexander J , Fry David W , Kraker Alan J 
Published: June 2007

SUMMARY1. Structure‐activity relationships are described for the inhibition of the tyrosine kinase activity (phosphorylation of a fragment of phospholipase Cg1) of the epidermal growth factor receptor (EGFR) by 4‐anilinoquinazolines. These compounds are competitive inhibitors at the ATP binding site.2. The preferred side chain is anilino‐, substituted at the 3‐position with small lipophilic groups. The quinazoline moiety is absolutely required for activity, but substituents on the quinazoline greatly modulate potency, with electron‐donating groups favoured. The most potent analogue, the 6,7‐dimethoxy derivative (compound 20), has an IC50 of 29 pmol/L and a very high selectivity for the EGFR over other tyrosine kinase enzymes.3. The present study shows that it is possible to identify small molecules that are very potent, yet highly selective, inhibitors of a single component of the growth signal transduction pathway in cells.
EFFECT OF ATRIAL NATRIURETIC FACTOR ON CORTICOTROPHIN‐RELEASING HORMONE‐INDUCED ADRENOCORTICOTROPHIN RELEASE IN THE MATURE OVINE FOETUS
Authors: McFarlane AC , Wintour EM 
Published: June 2007

SUMMARY1. Atrial natriuretic factor (ANF) and its analogues have been shown previously to inhibit corticotrophin‐releasing hormone (CRH)‐induced adrenocorticotrophin (ACTH) release, both in vivo and in vitro, and it has been suggested that ANF may be a, or the, physiological ACTH‐inhibitory factor. To determine whether ANF is relevant in the regulation of ACTH secretion in the ovine foetus, the present study examines the effect of ANF on CRH‐stimulated ACTH release in the mature ovine foetus.2. Five chronically cannulated foetuses, studied between 129 and 140 days of gestation (term 145–150 days), received intraarterial infusions of ovine CRH (4 μg/h) 120 min after the start of a sustained infusion of human ANF5–28 (10 μg/h) or saline (1.2 mL/h). Appropriate control experiments were performed, with foetuses receiving ANF or saline infusion only. CRH, ACTH, ANF and cortisol levels were measured by sensitive and specific radioimmunoassays. Each animal received all four treatments, with the order being randomized and 2–3 days being allowed between experiments.3. It was found that pretreatment (120 min) with ANF5–28 (at levels devoid of significant cardiovascular actions) had no effect on mean basal or peak ACTH and cortisol levels during CRH infusion. Given the current experimental parameters, these results suggest that ANF does not acutely modulate basal or CRH‐stimulated ACTH and cortisol release in the mature ovine foetus.
EFFECTS OF HISTAMINE AND 5‐HYDROXYTRYPTAMINE ON THE GROWTH RATE OF XENOGRAFTED HUMAN BRONCHOGENIC CARCINOMAS
Authors: Sheehan Peter FJ , Baker Timothy , Tutton Peter JM , Barkla David H 
Published: June 2007

SUMMARY1. The influence of histamine and 5‐hydroxytryptamine (5‐HT) antagonists and agonists on the volume doubling times (Td) of human bronchogenic carcinomas propagated as s. c. xenografts in immunosuppressed mice was examined.2. The H2‐receptor antagonists, cimetidine and ranitidine, increased Td.3. Treatment with the H2‐receptor agonist, 4‐methyl histamine, had no effect on Td.4. Co‐administration of 4‐methyl histamine and cimetidine abolished the effects of cimetidine.5. The 5‐HT2‐receptor antagonists, cinanserin and ketanserin, both increased Td.6. Treatment with the 5‐HT1/2‐receptor agonist quipazine (0.1 mg/kg, reflecting 5‐HT2 agonist activity) decreased Td, while a higher dose (10.0mg/kg) had no effect.7. The 5‐HT1/2‐receptor antagonist, methiothepin, decreased Td.8. The 5‐HT uptake inhibitor, fluoxetine, increased Td in one tumour line but not in another, while the 5‐HT releaser/depletor, fenfluramine, increased Td.9. Histamine may stimulate tumour growth through the histamine H2‐receptor, while the dominant effect of 5‐HT is 5‐HT1‐receptor inhibition.10. Tumour growth in some bronchogenic carcinomas may involve 5‐HT uptake mechanisms.