bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different effects of atrial and C-type natriuretic peptide on the urinary excretion of endothelin-1 in man
Authors: VILLA Giorgio LA , MANNELLI Massimo , LAZZERI Chiara , VECCHIARINO Sabrina , FEO Maria Laura DE , GUERRA Cristina TOSTI , BANDINELLI Renzo , FOSCHI Marco , FRANCHI Franco 
Published: August 2015

1.Following the observation that brain natriuretic peptide enhances the urinary excretion rate of endothelin-1, the relationship between natriuretic peptides and urinary endothelin-1 was further investigated. Six healthy volunteers received, on three different occasions, increasing doses of atrial or C-type natriuretic peptide (0, 2 and 4 ;pmol·min-1·kg-1 for 1 ;h each), or placebo.
2.Atrial natriuretic peptide caused significant increases in the urinary excretion of cGMP, sodium and endothelin-1, without affecting plasma endothelin-1, renal plasma flow, glomerular filtration rate and urine flow rate. C-type natriuretic peptide did not modify any of these parameters. During atrial natriuretic peptide infusion, urinary endothelin-1 directly correlated with plasma atrial natriuretic peptide, urinary cGMP and sodium excretion.
3.These results indicate that enhancement of the urinary excretion of endothelin-1 by natriuretic peptides is dose-dependent and somewhat related to their ability to bind to natriuretic peptide receptors A, activate guanylate cyclase and induce a natriuretic response.
Renal targeting of a non-steroidal anti-inflammatory drug: effects on renal prostaglandin synthesis in the rat
Authors: HAAS Marijke , MOOLENAAR Frits , MEIJER Dirk K. F. , JONG Paul E. DE , ZEEUW Dick DE 
Published: August 2015

1.Renal specific targeting of the non-steroidal anti-inflammatory drug naproxen was obtained by coupling to the low-molecular-mass protein lysozyme. A previous study showed that conjugation to lysozyme resulted in a 70-fold increase of naproxen accumulation in the kidney with a subsequent renal release of the active metabolite naproxen–lysine.
2.In the present study we questioned whether naproxen–lysozyme is active in the rat kidney, inhibiting the urinary excretion of prostaglandin E2 and renal sodium and water excretion in salt-restricted baseline conditions as well as during frusemide treatment.
3.A high dose of free naproxen (10 ;mg·day-1·kg-1) did not affect prostaglandin E2 excretion in baseline conditions (naproxen, 11±1 ;ng/8 ;h; vehicle, 13±4 ;ng/8 ;h), whereas sodium and water excretion were, respectively, 3.0 and 1.6 times lower in the naproxen group (P&lt; 0.05). Naproxen completely prevented the frusemide-induced increase (3-fold) in prostaglandin E2 excretion (naproxen 6.6±1.1 ;ng/8 ;h, vehicle 40±12 ;ng/8 ;h, P&lt; 0.005). Frusemide-stimulated natriuresis and diuresis were, respectively, 1.6 (P&lt; 0.05) and 1.8 times (P&lt; 0.005) lower in the naproxen group.
4.A dose of 2 ;mg·day-1·kg-1 lysozyme-conjugated naproxen did not affect prostaglandin E2 excretion in baseline conditions (conjugate, 18±2 ;ng/8 ;h; vehicle, 24±5 ;ng/8 ;h). The conjugate also had no effect on sodium and water excretion. However, the naproxen conjugate completely prevented the frusemide-induced increase (2-fold) in prostaglandin E2 excretion (conjugate, 16±3 ;ng/8 ;h; vehicle, 48±13 ;ng/8 ;h, P&lt; 0.05). Surprisingly, frusemide-induced natriuresis and diuresis were not affected by the conjugate.
5.In conclusion, a renal specific delivery of the non-steroidal anti-inflammatory drug naproxen using lysozyme results in an inhibitory effect on renal prostaglandin E2 synthesis but does not affect the excretion of sodium and water, in contrast to free naproxen.
Pulmonary response of normal human subjects to inhaled vasodilator substances
Authors: BRETT S. J. , CHAMBERS J. , BUSH A. , ROSENTHAL M. , EVANS T. W. 
Published: August 2015

1.Inhaled vasodilators such as nitric oxide and epoprostenol (prostaglandin I2) are now widely employed as supportive therapies to improve oxygenation and reduce pulmonary vascular resistance in patients with acute and chronic pulmonary hypertension. However, few data exist concerning their effects in normal individuals. The aim of this study was to characterize the response of the pulmonary circulation in normal individuals to inhaled nitric oxide and nebulized prostaglandin I2.
2.Eight healthy volunteers were exposed to inhaled nitric oxide (0, 20 and 40 ;p.p.m.) and nebulized prostaglandin I2 (10 ;μg/ml). Changes in effective pulmonary blood flow and diffusing capacity of the lung for carbon monoxide (TLCO) were measured using respiratory mass spectrometry. Bicycle ergometry was used to increase effective pulmonary blood flow as a positive control.
3.Exercise produced significant increases in both effective pulmonary blood flow and TLCO, but neither nitric oxide nor prostaglandin I2 produced significant changes in either parameter.
4.No significant change in pulmonary haemodynamics was demonstrated in response to inhaled nitric oxide or nebulized prostaglandin I2, using doses known to be effective in patients with acute and chronic pulmonary hypertension. These data suggest that the normal pulmonary vascular bed is not amenable to vasodilatation by inhaled drugs. The study further suggests that the normal pulmonary vasodilatation seen on exercise is not mediated pharmacologically, but is a secondary consequence to the mechanical effects of a rise in pulmonary blood flow. This study thus supports the view that there is no resting vasoconstrictor tone in the pulmonary vascular bed.
Transforming growth factor-β1 gene polymorphisms and coronary artery disease
Authors: SYRRIS Petros , CARTER Nicholas D. , METCALFE James C. , KEMP Paul R. , GRAINGER David J. , KASKI Juan C. , CROSSMAN David C. , FRANCIS Sheila E. , GUNN Julian , JEFFERY Steve , HEATHCOTE Kirsten 
Published: August 2015

1. A meta-analysis of 17 years of literature on erythrocyte Na+/Li+ countertransport (NLCT) and Na+/K+ co-transport (COT) measurements in relation to essential hypertension is presented. The analysis aimed to answer two questions: (i) Which clinical or laboratory variables influence NLCT and COT flux values? (ii) How useful are NLCT and COT measurements as a diagnostic aid in essential hypertension?
2. Regression analysis was performed on the mean flux values and relevant clinical and laboratory values. Studies in both normotensive and hypertensive subjects were stratified for variables which showed a significant association with the measured flux. For hypertensive subjects the studies were also stratified for medication. Means of strata were calculated after weighing the mean of a study by the inverse of its own variance and were compared in normotensive as well as hypertensive subjects using a t-test.
3. The analysis did not demonstrate systematic effects of laboratory variables for either NLCT or COT. It was found that essential hypertension, family history of hypertension, gender and antihypertensive medication are main determinants for the flux values of both transport systems. After stratification for these determinants, significant differences in weighed mean flux values between normotensive and hypertensive subjects were demonstrated. However, these differences are much smaller than the variance in the weighed mean flux values, suggesting the existence of other unknown variables that strongly affect the flux rates.
4. In conclusion, NLCT and COT measurements cannot be of diagnostic use in essential hypertension.
Increased myogenic tone precedes structural changes in mild experimental uraemia in the absence of hypertension in rats
Authors: SAVAGE Tessa , MCMAHON Aisling C. , MULLEN Adrian M. , NOTT Cathy A. , DODD Susan M. , TRIBE Rachel M. , YAQOOB Magdi M. 
Published: August 2015

1. Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodelling and the localization of atherosclerotic plaque. Uraemia is a proatherogenic process and is expected to be associated with impaired vascular reactivity.
2. To study this, 12 male Wistar rats were rendered uraemic by five-sixths nephrectomy and 12 control rats were sham operated simultaneously. After 8 weeks a tail-cuff systolic blood pressure was recorded, blood samples were taken and the animals killed. Isolated femoral arteries were dissected and mounted on a pressure myograph and myogenic tone was assessed over a range of intravascular pressures from 40 to 160 mmHg. Histologically the arteries were comparatively examined for gross morphology, calcification and deposition of collagen.
3. Biochemically the serum urea and creatinine were greater in the uraemic compared with the control rats (urea: 23.5±6 mmol/l and 6.8±01 mmol/l respectively, P not significant; creatinine: 130.7±13 mmol/l and 70.3±5 mmol/l respectively, P &lt; 0.01) but systolic blood pressure was the same in both groups (control, 97±1 mmHg; uraemic, 98±2 mmHg), compatible with mild uraemia.
4. Myogenic tone was significantly greater in uraemic vessels (7.3±1.8% versus 2.3±0.4% in control, P = 0.01). The actual vessel lumen diameter was also smaller in pressurized uraemic vessels compared with control vessels (471±30 μm versus 604±33 μm, P&lt; 0.01) after equilibration in physiological salt solution. However, when incubated in calcium-free physiological salt solution, the passive internal diameter was similar in uraemic vessels (538±25 μm compared with 595±31 μm in control). Histologically, there were no differences between the two groups.
5. We conclude that some aspects of vascular reactivity are altered in mild experimental uraemia as shown by a reduced internal lumen diameter and increased myogenic tone. Furthermore, these changes are apparent in the absence of hypertension and precede structural changes.
Chronic infusions of brain natriuretic peptide in conscious sheep: bioactivity at low physiological levels
Authors: CHARLES Christopher J. , ESPINER Eric A. , NICHOLLS M. Gary , RADEMAKER Miriam T. , RICHARDS A. Mark 
Published: August 2015

1. The circulating cardiac hormones atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have similar bioactivity, as judged by comparative short-term studies. However, no study has reported the effects of longer-term administration of BNP. Accordingly, we have compared the haemodynamic, hormonal and renal actions of chronic (4-day) administration of BNP and ANP (0.5 pmol·min-1·kg-1) in a vehicle-controlled study in normal conscious sheep.
2. BNP infusions raised plasma BNP levels within the physiological range (4 pmol/l increment, P&lt; 0.001) and increased cyclic GMP levels (P = 0.01). BNP infusions induced significant falls in right atrial pressure (P = 0.048), stroke volume (P = 0.014) and cardiac output (P = 0.003) associated with a rise in haematocrit (P = 0.001). There were no significant renal effects or changes in renin–aldosterone. By comparison, equimolar infusion of ANP induced a smaller increment in plasma ANP levels (2 pmol/l, P = 0.03) with qualitatively similar but statistically non-significant changes in plasma cyclic GMP and haemodynamic indices.
3. In conclusion, chronic low-dose infusions of BNP elevate plasma cyclic GMP levels and induce significant haemodynamic actions. This study provides evidence that subtle variations in circulating BNP levels, well within the physiological range, may be important in long-term cardiovascular control.
Gastrectomy osteopenia in the rat: the role of vitamin B12 deficiency and the type of reconstruction of the digestive tract
Authors: WOJTYCZKA A. , BERGÉ B. , RÜMENAPF G. , SCHWILLE P. O. , BALLANTI P. , SCHREIBER M. , FRIES W. , HOHENBERGER W. 
Published: August 2015

1. The mechanisms underlying gastrectomy osteopenia are not yet clear. The gastrectomy-associated cobalamin (vitamin B12) deficiency may favour osteopenia and skeletal fractures. Also, the exclusion of the duodenum from the food passage may contribute to gastrectomy osteopenia. To investigate this, rats were gastrectomized and the passage of nutrients restored either with the duodenum excluded (Roux Y) or included (Longmire). Sham-operated rats served as controls. In half of the rats in each gastrectomy group the serum B12 levels were normalized by parenteral administration of B12.
2. Four months post operation, both gastrectomy groups showed a similar degree of osteopenia. There was normal bone mineralization; serum levels of parathyroid hormone were normal, but decreased for 25-hydroxyvitamin D, and elevated for 1,25-dihydroxyvitamin D; in urine there was decreased pH and excessive hyperphosphaturia.
3 B12 therapy had no influence on any of the essential bone and mineral metabolic parameters.
4. We conclude that osteopenia in the gastrectomized rat (i) is not due to B12 or folic acid deficiency, calcium deficiency or secondary hyperparathyroidism; (ii) is independent of the type of anatomic reconstruction of the digestive tract; (iii) appears to be related to disturbed vitamin D, phosphorus and acid–base metabolism.
Lisinopril improves arterial function in hyperlipidaemia
Authors: LEE Alison F. C. , DICK John B. C. , BONNAR Clare E. , STRUTHERS Allan D. 
Published: August 2015

Endothelial function is defective in hypercholesterolaemia, and animal models have suggested that angiotensin-converting enzyme inhibitors may prevent arterial damage. We studied the effect of 6 months treatment with lisinopril on endothelial function in a group of patients with hypercholesterolaemia. Forty patients were studied. Forearm blood flow responses to acetylcholine and sodium nitroprusside were assessed by venous occlusion plethysmography. Subjects were then randomized in a double-blind fashion to receive either lisinopril, 20 mg/day (n = 20), or placebo (n = 20) for 6 months. Plethysmography was then repeated. Baseline variables between groups were comparable. In the lisinopril group blood pressure fell significantly [systolic: 145±4 to 128±4 mmHg (P< 0.001); diastolic: 84±2 to 74±2 mmHg (P< 0.001)]. An improvement was found in the vasodilatory response (expressed as a ratio of the infused/control arm) to acetylcholine, e.g. 3.33±0.3 (pre) versus 4.45±0.48 (post) at 30 μg/ml (P< 0.03), and also to nitroprusside, e.g. 3.0±0.2 (pre) versus 3.86±0.3 (post) at 3.2 μg/ml (P< 0.01). In the placebo group vasodilatation did not change significantly in response to acetylcholine, and nitroprusside responses were unchanged. The data presented suggest that 6 months of lisinopril therapy have a beneficial effect on arterial function in subjects with hyperlipidaemia. Further work should now investigate whether angiotensin-converting enzyme inhibitors are beneficial in reducing mortality and morbidity in hypercholesterolaemia.
Salt-sensitivity classification in normotensive adults
Authors: MATTES Richard D. , FALKNER Bonita 
Published: August 2015

The objectives of this study were to assess the reliability, sensitivity and specificity of salt-sensitivity classification in normotensive adults and to determine the predictive power of four clinical indices for salt-sensitivity. A total of 66 healthy, normotensive, free-living adults were administered 11-day salt-sensitivity diagnostic dietary salt challenges on two occasions to permit assessment of classification test–retest reliability. An oral glucose tolerance test, an acute saline loading test, gustatory testing and determination of salivary flow and sodium concentration were carried out to assess (by correlation analysis) their predictive power for salt-sensitivity. Following these procedures, 21 participants followed a reduced-sodium diet for 4 months, during which blood pressure was monitored monthly to allow evaluation of salt-sensitivity classification sensitivity and specificity. Regression was used to develop a predictive model for salt-sensitivity. Salt-sensitivity classification was not highly reliable (κ-value = 0.38), sensitive (0.73) or specific (0.60). No single index was highly predictive of classification status, but a model composed of five indices accounted for 92% of the variance in blood pressure response to acute salt challenge. The dietary salt challenge procedure used here for salt-sensitivity classification of normotensive adults had low test–retest reliability. While a battery of easily measured attributes may facilitate rapid salt-sensitivity classification, such a diagnosis provides only limited insight regarding blood pressure responsiveness to chronic dietary salt restriction in normotensive adults.
Faecal peritonitis causes oedema and neuronal injury in pig cerebral cortex
Authors: PAPADOPOULOS M. C. , LAMB F. J. , MOSS R. F. , DAVIES D. C. , TIGHE D. , BENNETT E. D. 
Published: August 2015

Encephalopathy is a common complication of sepsis. However, little is known about the morphological changes that occur in the brain during sepsis. Faecal peritonitis was induced in pigs that were killed 8 h later and frontal cortex samples were taken immediately after death. The tissue was investigated using light and electron microscopy and compared with frontal cortex samples taken from sham-operated controls. Septic pigs had 49.5% more perimicrovessel oedema than sham pigs. However, the tight junctions between cerebral microvessel endothelial cells appeared morphologically intact in both septic and sham pigs. Sepsis also resulted in neuronal injury, disruption of astrocytic end-feet and swollen, rounded erythrocytes. These morphological changes may be sufficient to underlie the clinical features seen in septic encephalopathy.
Co-expression of prepro-adrenomedullin with a putative adrenomedullin receptor gene in vascular smooth muscle
Authors: AUTELITANO Dominic J. , TANG F. 
Published: August 2015

The prepro-adrenomedullin (prepro-AM) gene encodes several biologically active peptides, including the potent vasodilator AM. At least part of the vasodilator action of AM appears to be mediated via interactions with receptors on vascular smooth muscle cells (VSMC); however, the specific receptors involved are not known. The aim of the present study was to identify putative AM receptor genes that are co-expressed with AM in cultured rat aortic VSMC that may mediate the actions of AM. AM mRNA was shown to be expressed in rat aortic VSMC cultures. In acute (4 h) secretion studies, only 20% of the total immunoreactive AM was intracellular, with the majority (80%) found in the medium, indicating active release of AM peptide from VSMC. Using highly specific ribonuclease protection analysis, mRNAs encoding three putative AM receptors [L1, calcitonin-receptor-like receptor (CRLR) and RDC1] were shown to be present at high concentrations in RNA extracts from lung. In cultured VSMC, however, whereas RDC1 mRNA was expressed at relatively high concentrations, transcripts encoding CRLR and L1 were not detected. The co-expression of prepro-AM mRNA with the RDC1 receptor implies that AM may act in a localized manner via this receptor to modulate VSMC function.
Dyspnoea, peripheral airway involvement and respiratory muscle effort in patients with Type I diabetes mellitus under good metabolic control
Authors: SCANO Giorgio , SEGHIERI Giuseppe , MANCINI Marco , FILIPPELLI Mario , DURANTI Roberto , FABBRI Alessandro , INNOCENTI Fabio , IANDELLI Iacopo , MISURI Gianni 
Published: August 2015

Dyspnoea and pulmonary dysfunction have recently been associated with Type I (insulin-dependent) diabetes mellitus. The putative role of altered pulmonary mechanics and of performance of inspiratory muscles in inducing dyspnoea has not been yet assessed in Type I diabetes. To better focus on this topic we evaluated nine patients with Type I diabetes mellitus, aged 19 to 48 years with good and stable metabolic control, without a history of smoking and microvascular complications, alongside a group of 14 healthy control subjects. In each subject, pulmonary volumes, static and dynamic compliance, pleural pressure swings (Pplsw), maximal inspiratory pressures (Pplsn), Pplsw(%Pplsn), a measure of respiratory muscle effort, and tension–time index [TTI = TI/TTOT×Pplsw(%Pplsn)] were measured (TI = inspiratory time;TTOT = total time of the respiratory cycle). All subjects were studied at baseline and during hypoxic rebreathing. Patients had normal pulmonary volumes. During hypoxic rebreathing, a normal change in respiratory muscle effort [ΔPplsw(%Pplsn)/ΔSaO2] and ΔTTI/ΔSaO2, and a lower change in tidal volume versus change in oxygen saturation [ΔVT(% vital capacity)/ΔSaO2], resulted in a higher ratio of respiratory effort to tidal volume [Pplsw(%Pplsn)/VT(% vital capacity)], a measure of neuroventilatory dissociation of the respiratory pump. Hypoxic dyspnoea, assessed by a modified Borg scale, showed a greater rate of rise (ΔBorg/ΔSaO2) and a greater increase for a given level of respiratory effort in patients. Moreover, neuroventilatory dissociation related to the expression of peripheral airway involvement, as assessed in terms of low dynamic compliance, and to concurrent change in dyspnoea sensation. Patients with Type I diabetes mellitus under good metabolic control and with normal lung volumes may have abnormal peripheral airway function. The latter is thought to be responsible for the association between dyspnoea sensation and neuroventilatory dissociation.
Up-regulation of nitric oxide production by interferon-γ in cultured peritoneal macrophages from patients with cirrhosis
Authors: BORIES P. N. , CAMPILLO B. , SCHERMAN E. 
Published: August 2015

We previously described a long-lasting overproduction of nitric oxide (NO) in cirrhotic patients with spontaneous bacterial peritonitis. The aim of the present study was to investigate the presence of the inducible NO pathway in peritoneal macrophages. Ascitic fluids were collected from 29 patients with cirrhosis, aged between 35 and 82 years. Peritoneal macrophages were isolated and cultured in the presence or absence of 1 μg/ml lipopolysaccharide and/or 500 units/ml interferon-γ (IFN-γ) for 6 days. NO production was measured as nitrate+nitrite (NOx), inducible NO synthase (iNOS) protein expression was analysed by immunocytochemistry and Western blot analysis using a specific anti-(human iNOS) antibody, and the catalytic activity of NOS was revealed by cytochemical staining for NADPH-dependent diaphorase. Cultured macrophages spontaneously released small amounts of NOx [median (10–90th percentile) of 18 separate experiments: 3.3 (0–8) μmol/l]. Addition of lipopolysaccharide alone or in combination with IFN-γ to the culture medium did not change the levels of NOx, while IFN-γ alone dramatically increased NO production [13.4 (3.5–28.3) μmol/l; P< 0.001]. Macrophages were stimulated by IFN-γ to a greater extent in patients with recent spontaneous bacterial peritonitis (n = 13) than in those in a stable clinical condition (n = 18) [19.8 (10.5–30.1) and 10.0 (3.2–14.5) μmol/l respectively; P< 0.001]. Macrophages freshly isolated or stimulated with IFN-γ expressed iNOS protein, as shown by Western blot and immunocytochemical analysis, and stained for NADPH diaphorase. Our findings demonstrate the presence of iNOS protein in peritoneal macrophages from cirrhotic patients. The role of IFN-γ appears to be a determinant for the up-regulation of NO production, particularly under conditions of infection. Therefore peritoneal macrophages producing large amounts of NO at the site of infection may contribute to maintaining splanchnic vasodilation in these patients.