bluuebunny/crossref_metadata_2025_split huggingface dataset:
VASOCONSTRICTOR RESPONSES TO COMPONENTS OF THE RENIN‐ANGIOTENSIN SYSTEM IN CYCLOSPORIN‐INDUCED HYPERTENSION IN THE RAT
Authors: Rolls K. A. , Phillips P. A. , Aldred K. , Hardy K. J. 
Published: June 2007

SUMMARY1. Since plasma renin activity is increased in cyclosporin A (CsA)‐induced hypertension in the rat, the role of the vascular renin‐angiotensin system (RAS) in CsA‐induced hypertension was investigated in rat mesenteric resistance vessels.2. Female Wistar rats received CsA (10 mg/kg per day, s.c.) or vehicle for 30 days. CsA treatment increased tail‐cuff systolic blood pressure (CsA treated 135 ± 3 mmHg vs control 125 ± 1 mmHg, P<0.0001).3. Mesenteric resistance arteries (200–300 μm) were isolated and mounted in a microvessel myograph. Concentration‐response curves to tetradecapeptide renin substrate (10‐11‐10−6 mol/L), angiotensin I (10‐l1‐10−6 mol/L) and angiotensin II (10‐12‐10−6 mol/L) showed no differences between CsA‐treated and control groups.4. Mesenteric vascular angiotensin‐converting enzyme (ACE) characteristics were determined by radioligand binding. There were no differences in the content or affinity of ACE between CsA‐treated and control rats.5. These results suggest that the mesenteric vascular RAS does not play a major role in CsA‐induced hypertension in the rat.
CYCLOSPORIN HYPERTENSION IN THE WISTAR RAT: ROLE OF UNINEPHRECTOMY
Authors: Martin Allison , Wong Kok‐Seng , Li Ming , Turner Steven W. , Whitworth Judith A. 
Published: June 2007

SUMMARY1. The effects of cyclosporin A (CyA) solution (1–50 mg/kg per day), CyA powder (5–20 mg/kg per day) and vehicle, and the effects of renal mass reduction on CyA induced hypertension, were examined in conscious Wistar rats.2. CyA solution consistently increased blood pressure at 5–20 mg/kg per day and the powder at 10–20 mg/kg per day. The vehicle had no consistent effect.3. Both CyA solution and powder inhibited gain in bodyweight. There was no consistent effect on food intake, water intake or urine volume. Plasma sodium (Na+), and Na+ and potassium (K+) excretion were reduced by CyA 20 mg/ kg per day.4. Renal function was impaired by CyA powder at 20 mg/kg per day and plasma renin activity (PRA) was increased by all doses of CyA powder.5. Thus, uninephrectomy did not potentiate CyA solution (5 mg/kg per day) induced increases in blood pressure and the effects of CyA do not appear to be a consequence of nephrotoxicity in Wistar rats.
HIGH INCIDENCE OF PRIMARY ALDOSTERONISM IN 199 PATIENTS REFERRED WITH HYPERTENSION
Authors: Gordon R. D. , Stowasser M. , Tunny T. J. , Klemm S. A. , Rutherford J. C. 
Published: June 2007

SUMMARY1. This study sought to assess the incidence of primary aldosteronism in 199 hypertensives who were normokalaemic and in whom the question of primary aldosteronism had never been raised.2. The screening test applied was the aldosterone to renin ratio in plasma, which was raised in 40 and normal in 159 patients. A second ratio was normal in 14 of these 40.3. Twenty‐two patients with two further raised ratios required fludrocortisone suppression testing. This has been completed in 17, and failure to suppress led to a diagnosis of primary aldosteronism in all.4. A dexamethasone suppression test (DST) excluded ACTH‐dependent hyperaldosteronism and laterality of aldosterone production was determined by adrenal vein sampling.5. Unilaterality in five patients led to adrenalectomy in four and spironolactone in one. Bilaterality in six patients led to spironolactone.6. This study so far provides a proven (minimum) incidence for primary aldosteronism of 8.5%, a probable incidence of 12.0% (including two raised ratios) and a possible (maximum) incidence of 13.0% (leaving out those with second ratio normal). Exclusion of hypokalaemic hypertensives will lead to an underestimation of the true incidence of primary aldosteronism.7. Based on this and other evidence, it is estimated that the incidence of primary aldosteronism in the ‘essential hypertensive’ population is between 5 and 15%, and is probably around 10%.
GENOTYPIC INFLUENCE ON PLASMA DIPEPTIDYL CARBOXYPEPTIDASE‐1 ACTIVITY IN HYPERTENSIVES
Authors: Morris Brian J. , Monaghan Judith C. , Perich Rose , Stokes Gordon S. , Jackson Bruce , Schrader Andrew P. 
Published: June 2007

SUMMARY1. Plasma dipeptidyl carboxypeptidase‐1 (DCP1; angiotensin I‐converting enzyme, kininase II; EC 3.4.15.1) tracks with the deletion allele in genotypes of a 287 bp insertion/deletion (I/D) polymorphism of its gene, DCP1, in healthy Caucasian populations. The aim of the present study was to see whether genotype has a similar influence on plasma DCP1 in hypertensives.2. The study involved 35 Caucasian patients with severe, familial essential hypertension, who were not being treated with DCP1 inhibitors, and 94 normotensives. Genotyping for the I/D polymorphism was performed by polymerase chain reaction and plasma DCP1 activity was measured by rate of hydrolysis of both [3H]‐Hip‐Gly‐Gly and Hip‐His‐Leu.3. Plasma DCP1 activity (nmol Gly‐Gly/min per mL; mean ± s.e.m.) was 67 ± 2, 82 ± 4 and 91 ± 6 in II, ID and DD hypertensives, respectively, which was similar to values of 68 ± 4, 82 ± 3 and 94 ± 3 in normotensives (P= 0.0001 by one‐way analysis of variance). Results for the His‐Leu assay indicated similar tracking with genotype.4. The Michaelis constant (μmol Hip‐Gly‐Gly/mL; mean ± s.e.m., n= 10) for DD subjects was the same as for II subjects (10.6 ± 1.6 vs 11.1 ± 2.3; P = 0.86).5. In conclusion, in severely hypertensive Caucasian subjects, plasma DCP1 activity is subject to a similar genotypic influence in hypertensives as has been reported previously in normotensives. Furthermore, the plasma DCP1 enzyme itself appears to be functionally similar for each genotype.
THE THROMBIN RECEPTOR
Authors: Dennington Peta M. , Berndt Michael C. 
Published: June 2007

SUMMARY1. The thrombin receptor has now been cloned and found to be a member of the G‐protein‐coupled seven‐transmembrane domain receptor family.2. The receptor has been detected directly in platelets, endothelial cells and smooth muscle cells and studies using receptor‐derived peptides have demonstrated that this receptor may be the one responsible for many of the actions of thrombin in platelets, endothelial cells, smooth muscle cells, fibroblasts, mesangial cells and neural cells.3. The receptor appears to be activated by the novel mechanism of cleavage by thrombin to yield a new N‐terminus which then interacts with the receptor as a tethered ligand to initiate cell activation.
HIGH LEVELS OF EXPRESSION OF NEUROPEPTIDE Y mRNA IN HUMAN PHAEOCHROMOCYTOMAS
Authors: Higuthi Hiroshi , Iwasa Atsushi , Yokokawa Kiyoshi 
Published: June 2007

SUMMARY1. Neuropeptide Y (NPY) gene expression in human phaeochromocytomas was investigated by measuring the levels of NPY mRNA and NPY‐immunoreactivity (NPY‐IR) in human phaeochromocytoma tissues in comparison with those in normal human adrenal tissues.2. The amounts of NPY mRNA and NPY‐IR in human phaeochromocytomas were 18 and 93 times higher, respectively, than those in normal adrenal glands. In contrast, beta‐actin gene expression was similar in human phaeochromocytomas to that in normal adrenal glands.3. The amount of NPY mRNA relative to total cellular RNA was 6‐fold higher in phaeochromocytoma tissues than in normal human adrenal medulla, suggesting increased NPY gene expression in the tumour cells.4. Induction of differentiation of PC12 rat phaeochromocytoma cells by compounds, such as dexamethasone and nerve growth factor, resulted in a marked increase in the NPY mRNA level.5. These findings suggest that NPY gene expression is increased in well‐differentiated human phaeochromocytoma cells. Its high level of expression could be responsible for the marked overproduction of NPY by this tumour.
POSSIBLE PARTICIPATION OF NMDA AND GLYCINE RECEPTORS BUT NOT GABAA RECEPTORS IN ENFLURANE‐INDUCED OPISTHOTONUS IN MICE
Authors: Komatsu Hisao , Nogaya Junko , Ueki Masaaki , Yokono Satoshi , Ogli Kenji 
Published: June 2007

SUMMARY1. We previously reported that volatile anaesthetics produce incidences of a transient opisthotonus in mice, a sign of CNS stimulation. This study was performed to investigate mechanisms by which enflurane‐induced opisthotonus (EIO) occurs.2. The effects of pretreatment of N‐methyl‐d‐aspartate (NMDA) antagonists dizocilpine (MK‐801; DIZ) and ketamine (KET), GABAA antagonists picrotoxin (PIC), pentylenetetrazol (PTZ) and glycine antagonist strychnine (STR) on the incidence of EIO were determined. Prior to exposure to 2.0% enflurane in air, male ddN mice were given intraperitoneal injections of 0.2 mL saline (control), 0.5–5.0 mg/kg DIZ, 20–80 mg/kg KET, 2.9 mg/kg PIC, 40.0 mg/kg PTZ and 0.75 mg/kg STR. After the injection, the behavioural state of the mice was observed for 20 min (the pre‐enflurane period). During the exposure to enflurane the time for immobilization, that is, anaesthetic induction time (IT), and the incidence of EIO were measured.3. Dizocilpine (1.0–5.0 mg/kg) and KET (80 mg/kg) significantly (P<0.01) reduced both the incidence of EIO and IT in a dose‐dependent manner. During the pre‐enflurane period DIZ produced incidences (5–40%) of transient seizures in a dose‐dependent manner, while KET did not induce them at all. The two GABAa antagonists had no detectable effect on the EIO. Strychnine significantly enhanced the EIO. These CNS stimulants resulted in a 3–10% incidence of transient seizure and/or opisthotonus during the pre‐enflurane period, but there was no correlation between DIZ‐induced seizure and EIO.4. These results suggest that the EIO is mediated by the NMDA and the STR‐sensitive glycine receptors, but not the GABAA receptor. We speculate that DIZ acts on the NMDA‐receptor and/or disrupts the balance between the inhibitory and the excitatory systems.
THE CONTROL OF HUMAN MOTOR UNITS
Authors: Miles Timothy S. 
Published: June 2007

SUMMARY1. The motor unit, consisting of a single motor neuron and the skeletal muscle fibres that it innervates, is the final output pathway of the motor system.2. Much is now known about the way that human motor neurons are recruited and controlled during voluntary and reflex movements. This review briefly summarizes some of the recent experimental data that has contributed to our present understanding. The review is largely limited to data obtained in human experiments. While much of what we know about the organization of the nervous system has come from studies of the anatomy and physiology of experimental animals, there are some questions that cannot be addressed in reduced animal preparations. The development of new techniques has made it possible to investigate the human nervous system at a level of detail that has not hitherto been possible.
IN VITRO INCUBATION OF BOVINE OVARIAN FOLLICLES: INDICATIONS FOR AN ACTIVE AND REGULATED RENIN‐ANGIOTENSIN SYSTEM
Authors: Hagemann A. , Nielsen A. H. , Avery B. , Poulsen K. 
Published: June 2007

SUMMARY1. The ovarian follicular renin—angiotensin system was investigated by using an in vitro incubation method, based on tissue incubation of individual bovine follicles.2. Very high and varying concentrations of active renin (median 18.0 GU/kg, range 2.1–107 GU/kg; n= 101) and prorenin (11.7 GU/kg, range <2.6–142 GU/kg; n = 101) existed in unincubated ovarian follicular tissue.3. Active renin and prorenin increased 35 and 959%, respectively, in follicular wall tissue and incubation medium during 72 h of in vitro incubation. The protein synthesis inhibitor cyclohexamide inhibited active renin and prorenin formation. No activation of prorenin occurred in incubation medium or follicular fluid in vitro. Active renin was degraded during incubation.4. Primarily prorenin but also active renin were secreted into the incubation medium. Secretion was directed both to the internal and external surface of the follicular wall.5. Follicle‐stimulating hormone (FSH) slightly stimulated the synthesis and secretion of prorenin in vitro.6. The synthesis and secretion rates of active renin and prorenin varied markedly between individual follicles.7. The finding of very high and varying concentrations of active renin in follicular wall tissues together with the formation and secretion of active renin during in vitro incubation provide further evidence for an active and regulated renin‐angiotensin system in ovarian follicles.
EFFECT OF INHIBITION OF NITRIC OXIDE SYNTHASE AND GUANYLATE CYCLASE ON HYDRALAZINE‐INDUCED VASODILATATION OF THE HUMAN FETAL PLACENTAL CIRCULATION
Authors: Leitch Ian M. , Read Mark A. , Boura Alan L. A. , Walters William A. W. 
Published: June 2007

SUMMARY1. The vasodilator effects of hydralazine in vitro, using the Krebs’ perfused human placental lobule was studied. Single placental lobules were bilaterally perfused (maternal and fetal sides 5 mL/min each, 95% O2, 5% CO2, 37°C) and changes in fetal arterial pressure (FAP) and venous outflow (VO) were recorded.2. Submaximal vasoconstriction was induced by KCl (20–50 mmol/L), which increased basal FAP from 22.8 ± 1.7 to 91.3 ± 3.9 mmHg (n =9, P<0.001), and decreased VO from 4.1 ± 0.6 to 0.2 ± 0.1 mL/min (n =6, P<0.01).3. Hydralazine caused vasodilatation (IC50 1.9 mmol/L, n = 9) and increased VO in the presence of KCl‐induced vasoconstriction.4. Infusion of Nω‐nitro‐L‐arginine (100 μmol/ L) to block nitric oxide synthase caused the basal FAP to increase from 30.9 ± 5.9 to 47.4 ± 6.7 (n =6, P<0.05) and significantly potentiated hydralazine‐induced vasodilatation (n =7, P<0.05).5. The soluble guanylate cyclase inhibitor LY 83583 (6‐anilino‐5,8‐quinolinedione) (1 μmol/L) significantly antagonized the vasodilatation produced by hydralazine (n =5, P<0.05).6. Thus, hydralazine appears to activate guanylate cyclase, leading to increased cyclic GMP in fetal arterial vascular smooth muscle to cause vasorelaxation. No evidence was obtained to suggest that hydralazine exerted its action by either releasing nitric oxide from endothelial cells in the placenta or acting as a nitric oxide donor.
THE EFFECT OF COCAINE AND DESIPRAMINE ON NEURONAL UPTAKE OF [3H]‐NORADRENALINE AND SENSITIVITY TO NORADRENALINE OF RAT MESENTERIC RESISTANCE ARTERIES
Authors: Byg Anne M. , Bund Stuart , Mulvany Michael J. , Aalkjær Christian 
Published: June 2007

SUMMARY1. The effects of cocaine and desipramine (DMI) on neuronal uptake (uptake1) of [3H]‐noradrenaline (NA) and isometric tension development to exogenous NA were assessed in mesenteric resistance arteries of Wistar rats.2. Both drugs concentration‐dependently inhibited [3H]‐NA uptake1, DMI being more potent than cocaine. The maximum inhibition produced by each drug was the same as that produced by denervation with 6‐hydroxydopamine. In denervated vessels there was no effect of cocaine on [3H]‐NA uptakel.3. Cocaine, in the same concentration range which caused inhibition of uptakel, increased the sensitivity to NA, while DMI, in a concentration range which inhibited uptake1, did not increase the sensitivity to NA and at high concentrations reduced the sensitivity and maximal response to NA. Since DMI affected responses to NA but not responses to vasopressin and potassium its effect is probably related to blockade of α1‐adrenoceptors.4. We conclude that the effect of cocaine on the sensitivity to NA reflects inhibition of uptakel in rat resistance arteries, while DMI cannot be used to assess the functional effect of uptakel in this preparation.
HAEMODYNAMIC ACTIONS OF A NITRIC OXIDE (EDRF) SYNTHESIS INHIBITOR IN CONSCIOUS BABOONS (Papio hamadryas)
Authors: Hennessy Annemarie , Whitworth Judith A. , Raymond Christopher J. , Phippard Andrew F. , Thompson John F. , Horvath John S. 
Published: June 2007

SUMMARY1. The haemodynamic effects of intravenous nitric oxide inhibitor, N‐nitro‐L‐arginine (NOLA), were examined in four conscious non‐restrained baboons (Papio hamadryas). Mean arterial pressure, (MAP), systemic vascular resistance (SVR) and cardiac output (CO) were measured at timed intervals up to 24 h after a bolus injection of NOLA.2. N‐nitro‐L‐arginine increased blood pressure in a dose‐dependent manner up to 9.5mg/kg. Increases in blood pressure were accompanied by increases in SVR and decreases in CO, with a significant fall in heart rate.3. One animal received 9.5 mg/kg NOLA and became unconscious, suggesting cerebral vasospasm.4. Vascular effects of nitric oxide contribute significantly to the regulation of arterial blood pressure under physiological conditions in the baboon.
ZATEBRADINE ATTENUATES CYCLIC AMP‐RELATED POSITIVE CHRONOTROPIC BUT NOT INOTROPIC RESPONSES IN ISOLATED, PERFUSED RIGHT ATRIA OF THE DOG
Authors: Sawaki Shoji , Furukawa Yasuyuki , Inoue Yasurou , Oguchi Takeshi , Chiba Shigetoshi 
Published: June 2007

SUMMARY1. Inhibition of If or Ica by zatebradine has been reported in mammalian SA nodal cells. We thus investigated whether zatebradine differentially attenuates the positive chronotropic and inotropic responses to norepinephrine, isoproterenol, NKH 477 (an adenylyl cyclase activator), 3‐isobutyl‐1‐methylxanthine (IBMX) and Bay k 8644 (a calcium channel agonist) in the isolated, blood‐perfused dog atrium.2. When zatebradine (0.03–1 μmol) decreased sinus rate from 104 ± 4.5 to 73 ± 4.9 beats/min dose‐dependently, it selectively attenuated the positive chronotropic but not inotropic responses to norepinephrine in a dose‐related manner. Zatebradine decreased the norepinephrine‐induced tachycardia (by approximately 80% from the control) more effectively than the spontaneous sinus rate (by approximately 30% from the control).3. Zatebradine similarly attenuated the positive chronotropic but not inotropic responses to isoproterenol, NKH 477 and IBMX. Fifty per cent inhibition doses of zatebradine (0.10–0.18 μmol) for the chronotropic responses to each substance were not significantly different.4. On the other hand, zatebradine attenuated neither positive chronotropic nor inotropic responses to Bay k 8644.5. We therefore suggest that zatebradine selectively attenuates the positive chronotropic but not inotropic responses to cyclic AMP‐related substances due to inhibition of If but not Ica in the dog heart.
GLYCERYL TRINITRATE ENHANCES THE ADENOSINE‐INDUCED INHIBITION OF PLATELET RESPONSES: A MECHANISM POTENTIALLY INVOLVED IN THE IN VIVO ANTI‐AGGREGATING EFFECTS OF ORGANIC NITRATES
Authors: Anfossi Giovanni , Massucco Paola , Piretto Valentina , Mularoni Elena , Cavalot Franco , Mattiello Luigi , Trovati Mariella 
Published: June 2007

SUMMARY1. The present study investigated the influence of the organic nitrate glyceryl trinitrate (GTN) on the anti‐aggregating effects of adenosine. We determined the effects of adenosine, GTN and their combination on platelet responses in platelet‐rich plasma and whole blood, and on intracellular levels of 3′,5′‐cyclic adenosine monophosphate (c AMP) and 3′,5′‐cyclic guanosine monophosphate (cGMP).2. Adenosine inhibited the in vitro platelet aggregation in response to different agonists in a dose‐dependent way through an elevation of intraplatelet cAMP levels. Effective adenosine concentrations were higher than those detectable under physiological conditions, but very close to levels achieved during myocardial ischaemia or haemorrhagic shock.3. GTN was able to decrease platelet responses influencing intraplatelet cGMP levels. Furthermore, the drug increased the inhibitory effects of adenosine and enhanced its effects on intraplatelet cAMP levels.4. The present data provides further evidence that compounds that increase intraplatelet levels of cGMP and cAMP act synergistically on the inhibition of platelet aggregability through the influence of increased cGMP levels on cAMP accumulation. The interplay between GTN and adenosine in the inhibition of platelet function could be effective during nitrate administration in the treatment of acute myocardial ischaemia when blood adenosine levels are significantly increased.
NEUTROPHIL PLATELET‐ACTIVATING FACTOR PRODUCTION AND ACETYLTRANSFERASE ACTIVITY IN CLINICAL ACUTE MYOCARDIAL INFARCTION
Authors: Strahan Mark E. , Graham Ross M. , Eccleston David S. , Sturm Marian J. , Taylor Roger R. 
Published: June 2007

SUMMARY1. Neutrophil function was studied in 10 males presenting with acute myocardial infarction (MI) within 6 h of onset and in 10 normal males. Neutrophil production of platelet‐activating factor (PAF), determined by bioassay, that of leukotriene B4 by HPLC, and the activity of an enzyme involved in the synthesis of PAF, acetyltransferase (AT), were measured before and after stimulation with opsonized zymosan and calcium ionophore, A23187.2. The neutrophil count was significantly raised at presentation in those with MI (8.2 ± 0.8 vs 2.8 ± 0.3 (s.e.m.) |MX 109 cells/L, P<0.001; t‐test, 18d.f.). Production of PAF per neutrophil in response to both stimulants was greater than normal in those with MI (zymosan: 21 ± 4 vs 12 ± 1ng/107 cells, P<0.05; ionophore: 174 ± 18 vs 113 ± 11ng/107 cells, P<0.02) despite normal leukotriene B4 production and depressed AT activity. By 7 days, the neutrophil count had significantly fallen but it remained greater than normal as did PAF production.3. Acute MI is associated with increased potential for production of PAF by neutrophils which may be important in the pathogenesis of MI.
ATRIAL NATRIURETIC HORMONES ORIGINATING FROM THE N‐TERMINUS OF THE ATRIAL NATRIURETIC FACTOR PROHORMONE
Authors: Vesely David L. 
Published: June 2007

SUMMARY1. Four peptide hormones consisting of amino acids 1–30 (Long Acting Sodium Stimulator), 31–67 (Vessel Dilator), 79–98 (Kaliuretic Stimulator) and 99–126 (Atrial Natriuretic Factor [ANF]) originate from the same 126 amino acid ANF prohormone.2. Each of these four peptide hormones circulates as a distinct peptide with vessel dilator and long acting sodium stimulator circulating at 10‐ to 24‐fold higher concentrations than ANF while kaliuretic stimulator circulates at a three‐fold higher concentration than ANF.3. Each of these peptide hormones is released with an increase in central volume causing stretch of the atrium of the heart and with rapid heart beats greater than 125 beats/min.4. Each of these peptide hormones lowers blood pressure, causes a diuresis and enhances sodium and/or potassium excretion.5. In disease states which retain sodium and water such as congestive heart failure (CHF), each of these atrial peptides increases in the circulation proportionately to the severity of sodium retention, but of the radioimmunoassays to each of these hormones only the vessel dilator radioimmunoassay differentiates between mild (class I) CHF and healthy individuals.
SECRETION AND RENAL EFFECTS OF ANF PROHORMONE PEPTIDES
Authors: Dietz John R. , Vesely David L. , Jr William R. Gower , Nazian Stanley J. 
Published: June 2007

SUMMARY1. Atrial natriuretic factor (ANF) and pro ANF peptides appear to be secreted simultaneously from the atria in response to atrial stretch.2. The major peptide forms secreted from rat atria appear to be ANF (pro ANF 99–126) as the primary C‐terminal peptide and pro ANF 1–30 as the primary N‐terminal peptide, as opposed to 1–67 or 1–98.3. The plasma concentrations of ANF and pro ANF 1–30 are increased by acute stimulation with blood volume expansion and the plasma levels of ANF and N‐terminal ANF prohormone peptides are chronically elevated by high salt diet.4. Pro ANF 31–67 produces a natriuresis which is not dependent on an increase in renal cGMP excretion, decreases in plasma renin activity (PRA) or elevations in plasma ANF concentration.