bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECT OF EXERCISE ON PLASMA ADRENOMEDULLIN AND NATRIURETIC PEPTIDE LEVELS IN MYOCARDIAL INFARCTION
Authors: Morimoto Atsushi , Nishikimi Toshio , Takaki Hiroshi , Okano Yoshiaki , Matsuoka Hiroaki , Takishita Shuichi , Kitamura Kazuo , Miyata Atsuro , Kangawa Kenji , Matsuo Hisayuki 
Published: June 2007

SUMMARY1. We investigated the effect of exercise on plasma adreno‐medullin, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations and studied the relationship between these peptides and haemodynamic parameters in nine patients with old myocardial infarction (MI) and in eight normal subjects.2. The exercise protocol consisted of two fixed work loads (40 and 80 W) for 4 min each and venous blood samples were taken at rest, during each exercise stage and after exercise while monitoring the mean arterial pressure (MAP) and heart rate (HR). In MI, pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), left ventricular end‐diastolic pressure (LVEDP) and cardiac output (CO) were measured throughout exercise.3. Adrenomedullin levels did not significantly increase with exercise. Adrenomedullin levels correlated with PAP and PCWP at rest (P < 0.05). Atrial natriuretic peptide levels correlated with PAP, PCWP and LVEDP throughout exercise (P < 0.05) but, on multiple regression analysis, PCWP correlated only with ANP (P < 0.01). Brain natriuretic peptide levels correlated with LVEDP throughout exercise (P < 0.01) and its increment correlated closely with basal BNP levels at rest (P < 0.01).4. These results suggest that adrenomedullin does not respond to the acute haemodynamic changes of exercise, whereas ANP responds to it and PCWP is the major stimulus factor. Brain natriuretic peptide responds to exercise in proportion to the basal synthesis of BNP in patients with left ventricular dysfunction and LVEDP may play a role in increasing BNP during exercise.
NON‐SPECIFIC INHIBITORS OF NITRIC OXIDE SYNTHASE CAUSE MYOCARDIAL NECROSIS IN THE RAT
Authors: Moreno Heitor , Nathan Luciana P. , Metze Konradin , Costa Soraia KP , Antunes Edson , Hyslop Stephen , Zatz Roberto , de Nucci Gilberto 
Published: June 2007

SUMMARY1. To study the effect of acute nitric oxide (NO) inhibition on the rat heart both in vitro and in vivo, male Wistar rats received a single bolus injection of saline, Nω‐nitro‐L‐arginine methyl ester (L‐NAME; 0.5,1.5,5.0,15.0 and 45.0 mg/kg) and D‐NAME (45.0mg/kg).2. Animals were killed 72 h after the bolus injection of L‐NAME and the hearts were removed and studied under light microscopy. In other groups of animals, saline, L‐NAME and D‐NAME were administered as above and the mean arterial blood pressure (MABP/carotid) was recorded. Furthermore, L‐NAME was also administered in the drinking water (20 mg/kg per day) for 72 h and animals were then killed and their hearts evaluated as described above. Hearts of control animals were perfused in vitro and coronary flow was measured following saline, L‐NAME (45 μg/heart) and D‐NAME (45 μ/heart).3. Areas of necrosis were observed in the left ventricle of animals that had received L‐NAME at 5.0, 15.0 and 45.0 mg/kg. Also, only doses higher than 1.5 mg/kg caused an important increase in MABP. The frequency and extent of the lesions paralleled the dose of L‐NAME administered and no lesions were observed in D‐NAME‐ and saline‐treated animals.4. The oral administration of L‐NAME also caused myocardial lesions similar to those described above, but the frequency and extent of these lesions were more discrete compared with those observed following 5.0 mg/kg, i.v., L‐NAME.5. Bolus injection of L‐NAME into control rat hearts in vitro resulted in a small and transient fall in coronary flow (17.2 ± 1.4 and 12.2 ± 1.2 mL/min before and after L‐NAME administration, respectively) within 30 s and this was followed 4.5 min later by a further (11.5 ± 1.6 mL/min) decrease. The administration of D‐NAME to control hearts caused no change in coronary flow.6. In conclusion, the acute inhibition of NO biosynthesis by L‐NAME causes myocardial necrosis. Both high levels of MABP and a small but significant reduction in coronary flow (associated or not) can be responsible for the lesions we found.
BENEFICIAL EFFECTS OF PENTOXIFYLLINE ON CYCLOSPORINE‐ INDUCED NEPHROTOXICITY
Authors: Kaputlu İrfan , Şadan Gülay , Karayalçin Binnur , Boz Adil 
Published: June 2007

SUMMARY1. Hypertension and renal failure are the two most common and severe complications due to cyclosporine A (CsA) therapy after transplantation. To determine whether an in vivo treatment with pentoxifylline (PTX) can prevent the toxic effects of CsA, three groups of rats were studied.2. The first group of rats (n = 11) received daily injections of CsA (15 mg/kg, i.m.) and PTX (45 mg/kg, i.p., b.i.d.), the second group of rats in= 11) was treated with CsA only and the third group of rats (n = 11) served as the control group (vehicle treatment).3. Whole blood CsA levels were similar in CsA + PTX and CsA alone groups. Although CsA treatment significantly increased mean arterial blood pressure (110.00 ± 2.48 nunHg; P<0.01), there was no significant increase in the PTX co‐treated group (104.09 ± 2.96 mm Hg) compared with initial values. In both the CsA alone and CsA + PTX groups the heart rate (365.45 ± 6.62 and 357.27 ± 7.23 b.p.m., respectively; P < 0.05) were found to be significantly higher than initial values. Serum creatinine levels increased significantly in the CsA alone group (1.40 ± 0.11 mg/dL; P < 0.01) compared with control values (0.81 ± 0.04 mg/dL). This increase was prevented by co‐treatment with PTX (serum creatinine 1.11 ± 0.10 mg/dL; P < 0.05). Total [99mTcl‐DTPA percentage renal uptake, as an index of glomerular filtration rate (GFR), was markedly and significantly lower in the CsA alone group (10.01 ± 0.79%; P < 0.01) than in the control group (18.19 ± 132%). Pentoxifylline co‐treatment attenuated this decrease compared with GFR in the CsA alone group (13.00 ± 0.75%; P < 0.01).4. These results suggest that the co‐administration of PTX with CsA may prevent the dose‐limiting toxic effects of CsA therapy.
URODILATIN (INN: ULARITIDE) AS A NEW DRUG FOR THE THERAPY OF ACUTE RENAL FAILURE FOLLOWING CARDIAC SURGERY
Authors: Meyer Markus , Wiebe Karsten , Wahlers Thorsten , Zenker Dieter , Schulze Frank‐Peter , Michels Peter , Forssmann Wolf‐Georg 
Published: June 2007

SUMMARY1. Acute renal failure is a severe complication following major cardiac surgery.2. The effects of urodilatin were evaluated in a randomized, double‐blind trial in patients suffering from incipient acute renal failure following cardiac surgery.3. In the urodilatin group (n= 7) acute renal failure was reverted, whereas in the placebo group (n= 7) six patients had to be haemofiltered or haemodialysed (P < 0.005).4. Urodilatin induced a rapid onset of diuresis in contrast to placebo‐treated patients, who remained oliguric.5. In the placebo group four of seven patients died while still on haemodialysis (mortality rate 57.1 %) during a postoperative follow‐up period of 60 days, while all patients treated with urodilatin survived.6. On the basis of these results it would appear that urodilatin is an effective drug for the treatment of incipient oliguric acute renal failure following cardiac surgery and for avoiding haemodialysis/haemoflltration.
RESPONSES OF THE DURAL CIRCULATION TO ELECTRICAL STIMULATION OF THE TRIGEMINAL GANGLION IN THE CAT
Authors: Lambert Geoffrey A. , Michalicek Jan , Regaglia Francesca 
Published: June 2007

SUMMARY1. In cats anaesthetized with a‐chloralose, electrical stimulation (ES) of the trigeminal ganglion produced a fall in blood pressure, a predominantly ipsilateral dilatation in the common carotid vascular bed and bilateral dilatation of the middle meningeal vascular bed. Section of the trigeminal root abolished these responses.2. Dilatation in the middle meningeal artery was not affected by section of the cervical sympathetic trunk nor by the section of the seventh cranial nerve trunk. The dilator response was abolished by section of the spinal cord at the C3 level and by intravenous administration of bretylium (10 mg/kg) or phentol‐amine (5 mg/kg). The response was significantly reduced by the prior administration of papaverine (10 mg/kg).3. Functional adrenalectomy by means of a snare placed around the nerves and blood vessels supplying the adrenal glands significantly reduced the response. Electrical stimulation of the trigeminal ganglion was accompanied by a fall in circulating levels of noradrenaline and serotonin.4. We conclude that ES of the trigeminal ganglion produces dilatation in the middle meningeal artery partly by autoregu‐lation during the trigeminal depressor response and partly by a reduction in the circulating levels of noradrenaline. It differs from the dilatation seen in the general carotid circulation and the cortical microcirculation, which is mediated by parasympathetic nerves. There is no evidence that antidromic release of neuropeptides from sensory nerve endings in the dura plays a part in the dilatation.
EFFECTS OF DIET ON MEASUREMENT OF NITRIC OXIDE METABOLITES
Authors: Wang Jian , Brown Mark A. , Tarn Sim Horn , Chan Maria C. , Whitworth Judith A. 
Published: June 2007

SUMMARY1. The present study investigated whether a low nitrate/nitrite diet could minimize variability in the measurement of endogenous plasma and urine nitric oxide (NO) metabolites, nitrate and nitrite (NOx) in normal subjects.2. Nitrate and nitrite concentrations were measured in plasma and urine as indicators of NO production in six subjects during a free diet and then during a low nitrate/nitrite diet for 6 days.3. The plasma concentration and 24 h urine NOx/creatinine ratio were significantly lower on the low nitrate/nitrite diet than on the free diet (P < 0.01). Nitric oxide production appeared to vary greatly within and between subjects, but these variations were substantially decreased by the fourth day of a low nitrate/ nitrite diet.4. Human plasma and urine NOx measurements should be determined after a low nitrate/nitrite diet for at least 4 days.
GENETIC FACTORS ASSOCIATED WITH ALTERED SODIUM TRANSPORT IN HUMAN HYPERTENSION: A TWIN STUDY
Authors: Nowson Caryl A. , McMurchie Edward J. , Burnard Sharon L. , Head Richard J. , Boehm Joanna , Hoang Hoa N. , Hopper John L. , Wark John D. 
Published: June 2007

SUMMARY1. Na+/H+ antiporter/exchange activity (NHE) in human cheek epithelial cells was assessed in 288 female twins and siblings. The genetic contribution of factors to NHE activity was assessed in 128 matched twin pairs (76 monozygotic (MZ); 52 dizygotic (DZ)).2. There was a small reduction in NHE with age and body mass index. The significant correlations (± their standard error (SE)) within MZ and DZ pairs of twins were 0.54 ± 0.08 and 0.26 ± 0.13, respectively, implying that genetic factors accounted for 54% of the variance in age‐adjusted NHE. There was no cross‐sectional relationship between NHE and measures of blood pressure. Based on within‐pair differences, however, there was a weak negative association (r= 0.22; P < 0.05) between mean arterial pressure and NHE.3. It remains to be determined whether NHE in cheek cells is associated with blood pressure tracking over time in young females.
PCR‐SSCP ANALYSIS OF THE GLUCOCORTICOID‐RESPONSIVE ELEMENT OF THE ATRIAL NATRIURETIC PEPTIDE GENE IN FAMILIAL PRIMARY OPEN‐ANGLE GLAUCOMA
Authors: Richardson Kimberley A. , Tunny Terry J. , Clark Charles V. 
Published: June 2007

SUMMARY1. Familial primary open‐angle glaucoma (POAG) is a heterogeneous disease of unknown aetiology and the elucidation of the underlying genetic mechanisms contributing to phenotypic expression will be essential if earlier diagnosis of at‐risk individuals and more specific medical treatment can be achieved. In a significant percentage of patients with POAG, intraocular pressure increases in response to topical ocular glucocorticoids.2. Atrial natriuretic peptide (ANP) assists in the regulation of intraocular pressure levels and binding of the glucocorticoid receptor dimer to the glucocorticoid‐responsive element in intron 2 of the ANP gene has been shown to increase ANP mRNA levels in vitro. We amplified and examined this sequence in the ANP gene by PCR‐SSCP analysis in 100 patients with familial POAG and in 60 normal control subjects. No base alterations in the amplified product were found.3. Thus, the present study found no evidence for an alteration in the sequence of the glucocorticoid‐responsive element of the ANP gene that could alter ANP gene transcription in patients with familial POAG. The mechanism responsible for the increase in intraocular pressure levels in response to glucocorticoids is most likely independent of the glucocorticoid‐responsive element in the ANP gene.
NITRIC OXIDE SYNTHASE INHIBITION IN A SPONTANEOUSLY HYPERTENSIVE RAT MODEL OF DIABETIC NEPHROPATHY
Authors: Wessels J. , Peake P. , Pussell BA , Macdonald GJ 
Published: June 2007

SUMMARY1. To investigate the role of nitric oxide (NO) in diabetic nephropathy the effect of nitric oxide synthase (NOS) inhibition by NG‐nitro‐L‐arginine methyl ester (L‐NAME) was observed in a streptozotocin diabetic spontaneously hypertensive rat (SHR) model.2. Two groups of SHR (n= 8) with streptozotocin‐induced diabetes were studied. One group was given L‐NAME 5mg/kg body weight per day in the drinking water for 8 weeks while both groups received daily subcutaneous injections of Ultratard insulin. Creatinine clearance, urinary protein excretion, urinary nitrate concentration and systolic blood pressure were measured at fortnightly intervals. Rats were killed at 8 weeks and plasma angiotensin II (AngII) was measured by radioimmunoassay.3. Renal function (endogenous creatinine clearance) remained stable in both groups. In the L‐NAME group, however, there was a progressive increase in proteinuria that was highly significant at 6 weeks (22.1 ± 2.9 compared with 6.5 ± 0.7 mg/ 24 h per 100 g in control SHR diabetic rats P < 0.001).4. Systolic blood pressure was significantly elevated in the L‐NAME group throughout the study compared with the control group.5. Plasma AngII was significantly elevated in the L‐NAME group compared with controls (42.8 ± 10.3 vs 15.1 ± 1.9 pmol/L, respectively; P < 0.05).6. Activation of the renin‐angiotensin system may account, at least in part, for the resulting vasoconstrictor activity with chronic nitric oxide depletion.
ASSOCIATION ANALYSIS OF SIX CANDIDATE GENES IN A SAMPLE OF AUSTRALIAN HYPERTENSIVE PATIENTS
Authors: Huggard PR , Summers KM , West J. , West MJ 
Published: June 2007

SUMMARY1. Essential hypertension is characterized by increased vascular resistance due to narrowing of the small arterioles. This may be influenced by vasoactive substances, cell growth and vascular remodelling.2. A sample of Australian hypertensive and normotensive subjects was investigated for association with genetic markers which are candidates for a role in blood pressure (BP) regulation due to potential effects on vascular diameter.3. The six markers used were for genes encoding vasoconstrictors, growth factors and a structural protein of the extracellular matrix.4. No significant association of any of the markers used was found with BP status in this sample of patients.
EFFECTS OF OESTROGEN AND PROGESTERONE ON AGE‐RELATED CHANGES IN ARTERIES OF POSTMENOPAUSAL WOMEN
Authors: Liang Yu‐Lu , Teede Helena , Shiel Louise M. , Thomas Adrian , Craven Robyn , Sachithanandan Nirupa , McNeil John J. , Cameron James D. , Dart Anthony , McGrath Barry P. 
Published: June 2007

SUMMARY1. Hormone replacement therapy (HRT) with oestrogen or oestrogen plus progestin may have different effects on arterial structure and function. To examine this question, carotid artery intima‐medial thickness (IMT) and indices of systemic and carotid arterial compliance were measured in groups of older men, postmenopausal women not on HRT (non‐HRT) and those women on long‐term HRT with oestrogen alone (HRT‐E) or oestrogen plus progestin (HRT‐EP).2. Sixty men, 90 postmenopausal women taking HRT and 91 not taking HRT participated in the study. The groups were similar for age, body mass index, numbers of smokers, physical activity, alcohol intake and blood pressure.3. Plasma total cholesterol was reduced and high‐density lipo‐protein‐cholesterol was increased in the HRT group compared with the non‐HRT group; low‐density lipoprotein‐cholesterol, triglyceride and lipoprotein (a) values were similar in these two groups. Results for HRT‐E and HRT‐EP subgroups were similar.4. Carotid IMT was significantly reduced in the HRT group compared with men and non‐HRT groups. Results for HRT‐E and HRT‐EP subgroups were similar.5. Mean systemic arterial compliance (SAC) was significantly greater in men than in women and was related to age; SAC was higher in both HRT‐E and HRT‐EP groups compared with the non‐HRT group. Indices of carotid stiffness were similar in men and in non‐HRT groups. The HRT‐EP group showed increased carotid stiffness compared with the HRT‐E group.6. There is an apparent protective effect of long‐term oestrogen therapy on carotid IMT and age‐related changes in arterial stiffness. Progestin does not alter the IMT effects but may adversely influence arterial stiffness.
DRUG‐MEDIATED INACTIVATION OF CYTOCHROME P450
Authors: Murray Michael 
Published: June 2007

SUMMARY1. Multiple forms of cytochrome P450 (CYP) catalyse the oxidation of chemicals of endogenous and exogenous origin, including drugs, carcinogens, steroids and eicosanoids. However, this unusual low substrate specificity also makes CYP susceptible to inhibition by a wide range of drugs, leading to pharmacokinetic interactions of potential clinical significance.2. Some drugs are converted by CYP to reactive metabolites that bind covalently to sites within the active centre of the same CYP. Such mechanism‐based inhibition leads to CYP inactivation or complexation. These processes give rise to long‐term effects on drug pharmacokinetics, as the inactivated or complexed CYP must be replaced by newly synthesized CYP protein.3. Drugs that inactivate CYP generally possess recognizable functional groups that are oxidized to reactive products. Thus, drugs with side chains containing unsaturated carbon‐carbon bonds and furan ring systems are associated with CYP inactivation. Nitrogen‐containing systems may also inactivate CYP.4. Metabolites formed from drugs containing alkylamino and methylenedioxy functionalities can trap CYP as inert complexes without eliciting inactivation. However, the functional effects of inactivation and complexation on drug pharmacokinetics are indistinguishable. Drugs that elicit CYP complexation include the first generation macrolide antibiotics, but newer analogues appear much safer. Some antidepressants, antiepileptics and tuberculostatic agents have been associated with CYP complexation.
CELL‐SPECIFIC PROTEIN AND GENE EXPRESSION IN THE JUXTAGLOMERULAR APPARATUS
Authors: Barajas Luciano 
Published: June 2007

SUMMARY1. The juxtaglomerular apparatus (JGA) consists of a tubular component, the macula densa (MD), attached to a vascular component consisting of the afferent and efferent arterioles and the extraglomerular mesangium. The JGA is richly innervated by sympathetic fibres.2. The MD is morphologically, histochemically and functionally different from the ascending thick portion of the loop of Henle where it is located.3. The vascular component includes the vascular smooth muscle cells of the arteriole, the renin‐producing cells or juxtaglomerular cells, extraglomerular mesangial cells (Goormagh‐tigh cells) and endothelial cells. They are coupled by gap junctions.4. Physiological evidence indicates that the composition of tubular fluid at the MD regulates renin secretion and glomerular haemodynamics and that the JGA is important in the maintenance of body salt‐water homeostasis. Evidence suggests that the MD exerts its action on the vascular component through a paracrine mechanism.
WATER CHANNELS AND UREA TRANSPORTERS
Authors: Wintour E Marelyn 
Published: June 2007

SUMMARY1. It now appears that when water crosses an endothelium which is not fenestrated, or an epithelium with tight junctions, it does so rapidly, and with low energy cost, only if the cell membrane contains an adequate number of specific water channels, encoded by one of at least six different genes.2. The water channel genes so far cloned encode a series of integral membrane proteins called aquaporins, all of approximately 30kDa (265–282 amino acids), in the unglycosylated state. All but one (AQP3) are specific water channels and all but one (AQP4) are inactivated by mercurial compounds.3. Aquaporin 0 is the major (60%) intrinsic protein (MIP) of lens fibre cells of the eye. Mutations in this gene are associated with cataract formation in mice.4. Aquaporin 1, also called CHIP‐28, exists in the membrane as a homotetramer, and is present in red blood cells, the choroid plexus, the proximal tubule and descending limb of the loop of Henle in the kidney as well as in many other sites. Surprisingly, no pathological consequence is known in patients lacking a functional AQP1 gene.5. Aquaporin 2, also called WCH‐CD, is the water channel of the principal cell of the cortical and medullary collecting duct, and is located in cytoplasmic vesicles unless arginine vasopressin is acting, when it is translocated to the apical membrane by synaptobrevins or vesicle associated membrane protein 2 (VAMP2). Lack of a functional AQP2 gene leads to a rare form of nephrogenic diabetes insipidus.6. Aquaporins 3, 4, and 5 are located in many tissues—AQP3 and AQP4 being in the basolateral membrane of the renal cortical and medullary principal cell, as well as in the gastrointestinal tract (AQP3) and the brain (AQP4).7. Four sequences are known for urea transporters HUT11—the urea transporter of the human red cell membrane, and HUT2, rUT2, rbUT2—the arginine vasopressin inducible urea transporters of the human, rat and rabbit kidney. They are specifically permeable to urea, not to water, and are claimed to be inhibited by phloretin.8. The water channel proteins contain six membrane‐spanning regions, whilst the urea transporters are thought to contain at least 10 membrane spanning segments.9. Very little work has examined the ontogeny of these proteins, except in the rat, and virtually nothing is known of the expression of these genes in pregnancy or in any disorder of fluid balance in the mother or foetus.
RE‐EVALUATION OF THE SA GENE IN SPONTANEOUSLY HYPERTENSIVE AND WISTAR‐KYOTO RATS
Authors: Ishinaga Yuji , Nabika Toru , Shimada Toshio , Hiraoka Junko , Nara Yasuo , Yamori Yukio 
Published: June 2007

SUMMARY1. To investigate whether the difference in the SA gene expression in the kidneys is causally related to the pathogenesis of hypertension, we reassessed the expression of the SA gene in the kidneys of the spontaneously hypertensive rat (SHR), its stroke‐prone substrain (SHRSP) and Wistar‐Kyoto (WKY) rat from different sources (SHR/Izm, SHRSP/Izm and WKY/ Izm from Izumo colony; SHR/Crj and WKY/Crj from Charles River Laboratories).2. At the age of 5 weeks, high levels of the SA mRNA were expressed in the kidneys of SHRSP/Izm, SHR/Izm, SHR/Crj and WKY/Izm, while very low levels of the SA mRNA were observed in those of WKY/Crj. At the age of 8 weeks, the expression of the SA mRNA in the kidneys of WKY/Izm was at the same level as in those of SHRSP/Izm and two SHR strains.3. Four genetic markers at the SA locus, an StuI restriction fragment length polymorphism and three microsatellite markers, were not polymorphic among Izumo strains of SHR, SHRSP and WKY rats.4. In situ hybridization showed strong signals of the SA mRNA in the renal proximal tubules, while no positive signals were detected in the glomeruli.5. Because WKY/Izm has normal blood pressure, our observations indicate that a simple difference of the SA gene expression in the kidney cannot be an explanation for the difference of blood pressure between SHR(SP)/Izm and WKY/Izm.