bluuebunny/crossref_metadata_2025 huggingface dataset:
VASOCONSTRICTOR RESPONSES TO POLYMORPHONUCLEAR LEUCOCYTES FROM ATHEROSCLEROTIC RABBITS
Authors: Sobey Christopher G. , Hart Joanne L. , Woodman Owen L.
Published: June 2007

1. The vascular contractile effects of polymorphonuclear leucocytes (PMN) isolated from control rabbits and from rabbits made atherosclerotic by 1% cholesterol feeding for 8 weeks were examined.

2. Rings of control rabbit thoracic aorta with or without endothelium were mounted at 2g tension in 10 mL organ baths and were submaximally contracted by phenylephrine (0.1 μmol/L). After 30 min incubation at 37° C, the supernatant of PMN (5X107/mL, in Tyrode solution containing 0.25% bovine serum albumin) was obtained by centrifugation for addition to the vascular preparation.

3. Control PMN supernatant (443 μL) caused contraction (0.58±0.15g, n= 11) of phenylephrine‐contracted aortic rings, which was prevented by removal of the endothelium (0.11 ± 0.07g, n= 5, P<0.05). However, the control PMN supernatant had no contractile effect on aortic rings at resting tension (0.00 ± 0.00g, n= 8).

4. By comparison, atherosclerotic PMN supernatant (443 μL) caused a significantly greater contraction of the aortic rings (1.41± 0.13g, n= 9, P<0.05 vs control PMN supernatant) that was only partly inhibited by removal of the endothelium (0.45 ± 0.20g, n= 9, P<0.05). Moreover, PMN supernatants from four of seven atherosclerotic rabbits contracted aortic rings at resting tension (3.5 ±1.4g, n= 7).

5. These results suggest that the release of a stable vasoconstrictor substance(s) by PMN is enhanced under conditions of atherosclerosis. The constrictor action of this substance(s) appears to be greater in the presence of a functional endothelium, and part of its action may involve inactivation of endothelium‐derived nitric oxide.
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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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.
EFFECTS OF ANF PROHORMONE PEPTIDES IN CONSCIOUS PRIMATES
Authors: Benjamin Bruce A.
Published: June 2007

1. Recent studies suggest that amino‐terminal peptides from the atrial natriuretic factor (ANF) prohormone are natriuretic.

2. The effects of pro ANF 31–67 and ANF 99–126 on renal function were studied in conscious non‐human primates (Macaca fuscicularis).

3. Results show that pro ANF 31–67 and ANF 99–126 are diuretic and natriuretic and that when the two peptides are given in combination sodium excretion increases in an additive fashion.

4. These results indicate that multiple peptides from the ANF prohormone are natriuretic. Furthermore, these findings suggest that the combined action of these peptides causes the natriuresis that occurs after the release of endogenous atrial peptides.
REFLEX REGULATION OF HORMONAL RESPONSES DURING PREGNANCY
Authors: Keller‐Wood Maureen
Published: June 2007

1. During pregnancy in most species, the resting levels of plasma angiotensin II, plasma ACTH (corticotropin) are increased. The concentration of vasopressin is also increased relatively to the osmolality in rats and in humans.

2. In the pregnant state mean arterial pressure is decreased, despite an increase in blood volume. Vasopressin and ACTH responses to hypotension are altered in pregnant ewes; the relationship between mean arterial pressure and vasopressin or ACTH response is shifted to the left, consistent with a change in set‐point for regulation of mean arterial pressure. The vasopressin and cortisol responses to hypotensive haemorrhage are also altered in the pregnant dog; in this case the slope of the relation between mean arterial pressure and hormone response is decreased.

3. The decrease in hormone responses to hypotension is stimulus‐specific; ACTH responses to hypoglycaemia are increased in the pregnant ewe and AVP responses to hyperosmolality are not altered in the pregnant ewe.

4. The heart rate responses to hypotension are also decreased in pregnant ewes, consistent with the observation that baro‐reflex responses are decreased in the pregnant rat.

5. The data suggest that a change in regulation of arterial pressure alters the hormonal responses to hypotension in the pregnant state.
LEFT VENTRICULAR FUNCTION FOLLOWING THROMBOLYTIC THERAPY FOR MYOCARDIAL INFARCTION
Authors: French John K. , White Harvey D.
Published: June 2007

1.The aim of this study was to evaluate the utility of measurement of left ventricular function in assessing the efficacy of thrombolytic agents.

2.All published studies were reviewed.

3.The major effect of the introduction of thrombolytic therapy on mortality after myocardial infarction has been a dramatic decrease in the number of patients dying from cardiac failure. In the thrombolytic era, left ventricular function has remained the most important prognostic factor after recovery from acute myocardial infarction. There are three trials with the statistical power to evaluate left ventricular function, where both left ventricular function and survival were improved compared to placebo or control treatment. The recent Global Utility of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) Trial supports these findings, with left ventricular function being strongly correlated with mortality reduction. Left ventricular function, measured at 90 min either as ejection fraction, end‐systolic volume or infarct zone contractility, closely correlated with 30 day mortality, P< 0.01.

4. Left ventricular function remains an important factor in the evaluation of the efficacy of different thrombolytic and adjuvant regimens.
CENTRAL NERVOUS SYSTEM ACTIVITY OF RHAZYA STRICTA (DECNE) IN MICE
Authors: Ali B. H. , Bashir A. K. , Banna N. R. , Tanira M. O. M.
Published: June 2007

1. The effects of orally administered aqueous lyophilized extract of the leaves of Rhazya stricta (2, 4 & 8 g/kg) on aspects of nervous system function were investigated in mice.

2. In three antinociceptive tests (hot plate, abdominal constriction, and warm water tail flick tests), the extract exhibited dose‐dependent and significant antinociceptive activity. Naloxone was ineffective in antagonizing the analgesic effect of Rhazya stricta on tail‐flick and abdominal constriction tests, possibly indicating that this effect occurs via non‐opiate pathways.

3. Pretreatment of mice with the xenobiotic metabolizing enzymes inhibitor cimetidine (50 mg/kg) did not significantly alter the antinociceptive action of the extract, indicating that the effect is probably due to the parent compound(s) present in the extract and not to metabolites thereof.

4. R hazy a stricta produced dose‐dependent sedation, decreased motor activity, and impaired motor control. Time spent on a rotarod treadmill was significantly decreased after treatment with the extract.

5. R hazy a stricta extract (8 g/kg) produced a degree of sedation comparable to that produced by diazepam (5–10 mg/kg), and also significantly increased the reaction time of the tail‐flick test, an action which was not produced by diazepam.

6. Administration of R. stricta extract potentiated pento‐barbitone sleeping time in a dose dependent manner. The extract did not significantly antagonize picrotoxin induced convulsions. The extract (4 and 8 g/kg) significantly decreased the rectal temperature of normothermic and hyperthermic mice.

7. Pretreatment with R. stricta extract (8 g/kg) completely prevented the occurrence of aggressive behaviour in male mice.

8. It is concluded that the crude extract of R. stricta has central nervous system depressant properties.
EVIDENCE OF AN ADENOSINE‐DEPENDENT MECHANISM IN THE HYPOTENSIVE EFFECT OF l‐ARGININE IN MAN
Authors: Pasini Franco Laghi , Frigerio Carlo , Blardi Patrizia , Domini Lorenzo , Giorgi Laura De , Borgogni Giovanna , Pecchi Silvio , Cati Graziella , Franchi Massimo , Volpi Luciana , Perri Tullio Di
Published: June 2007

1. The hypothesis that endogenous adenosine could play a role in the haemodynamic response to l‐arginine is investigated.

2. The study has been divided into two parts. The first part was a single blind, randomized, placebo‐controlled study in which L‐arginine i.v. infusion (0.07 mmol/kg per min) in five healthy volunteers caused a significant fall in systolic (‐14.2%, from 129.0 ± 8.2 to 110.6 ± 8.5 mmHg; F= 62.89, P<0.0l), diastolic (‐16%, from 80.0 ± 7.9 to 67.2 ± 7.0 mmHg; F= 18.97, P < 0.0l) and mean (‐15.5%, from 96.4 ± 6.7 to 81.4 ± 6.5 mmHg; F= 28.78, P< 0.01) arterial blood pressure, with a concomitant increase of plasma adenosine concentration (from 244.0 ± 32.2 to 637.0 ± 43.4 nmol/L; F= 79.3 P<10.01). Maximal effects were obtained at the end of L‐arginine infusion: haemodynamic parameters returned to basal values in about 30 min while adenosine concentrations normalized in about 15 min. Saline infusion had no effect on these parameters.

3. In the second study the effect of L‐arginine i.v. infusion on arterial blood pressure, lower limb blood flow and plasma adenosine, before and after theophylline treatment (1000 mg/day for 3 days, p.o.) was examined. In 10 healthy volunteers the i.v. infusion of l‐arginine (0.07 mmol/kg per min) was followed by the same haemodynamic changes as reported above and by a Significant increase in lower limb blood flow (+ 36.7%, from 2.18 ± 0.40 to 2.98 ± 0.71mL/min/lOOmL;t = 4.61, P< 0.01). Pretreatment with theophylline, an adenosine‐receptor antagonist, did not affect basal values of arterial pressure, lower limb blood flow and adenosine concentration. The pretreatment with theophylline reduced maximal decrease in systolic pressure (‐ 8.2 vs ‐15%), in mean pressure (‐ 9.9 vs ‐13.7%) and maximal increase in lower limb blood flow (+19 vs + 37%) caused by i.v. infusion of l‐arginine (0.07 mmol/kg per rnin). Such a treatment allowed a progressive restoration of basal blood pressure values and of blood flow, during the second half of l‐arginine infusion. This observation was confirmed by the analysis of the area under the curves (AUC). A significant difference in AUC values before and after treatment was obtained for systolic pressure (t = 8.25, P< O.Ol), mean pressure (t= 6.67, P<0.0l) and blood flow (t= 2.31, P<0.05).

4. Theophylline study suggested that the endogenous adenosine increase is sufficient to participate at least in part in the haemodynamic changes caused by l‐arginine and that it is involved in a secondary response to l‐arginine.
CYCLOSPORINE A HEPATOTOXICITY: EFFECT OF PROLONGED TREATMENT WITH CYCLOSPORINE ON BILIARY LIPID SECRETION IN THE RAT
Authors: Galán Ana I. , Fernández Emilio , Morán Dominica , Muñoz Maria E. , Jiménez Rafael
Published: June 2007

1. The effects of cyclosporine A (CyA) treatment on liver morphology, bile flow and biliary secretion of bile acid, cholesterol and phospholipid and some plasma biochemical indicators of liver function were examined.

2. Wistar rats were treated i.p. with 10 or 20 mg of CyA/kg per day for 1, 2, 3 or 4 weeks.

3. Treatment increased bile acid and bilirubin plasma concentration. Bile flow and biliary secretion of bile acid, cholesterol and phospholipid were reduced in CyA‐treated animals.

4. All these effecs of the drug appeared at 1 week after the start of treatment and were enhanced during prolonged treatment. Cyclosporine A‐induced cholestasis was due to a decrease in both the bile acid‐dependent and ‐independent fractions of bile flow.

5. The reduction in cholesterol and phospholipid biliary output may be secondary to the inhibition of the hepatobiliary flux of bile acid; however, perturbations in the removal of lipids from the canalicular membrane as well as intracanalicular interaction between CyA and lipid vesicles/micelles could also be involved.
NITRIC OXIDE: ROLE IN NEUROTOXICITY
Authors: Dawson Valina L.
Published: June 2007

1. Nitric oxide (NO) is a novel neuronal messenger molecule which interacts with surrounding neurones, not by synaptic transmission but by diffusion between cells.

2. No is produced following stimulation of the enzyme, NO synthase (NOS). After synthesis, NO exerts its biological actions by diffusion to the site of action. Therefore, the way to regulate the physiological actions of NO is to regulate NOS.

3. NOS is activated by the influx of calcium from glutamate‐activated N‐methyl‐D‐aspartate receptors. Overactivation of these receptors leads to overproduction of NO and neuronal cell death.

4. NOS can be regulated at the catalytic site, at the flavoproteins, at the calmodulin site and by phosphorylation.

5. In excess, NO is toxic to neurones. This toxicity is mediated largely by an interaction with the superoxide anion, presumably through the generation of the oxidant, peroxynitrite.

6. NO or peroxynitrite‐mediated neuronal injury involves the activation of the nuclear protein, poly(ADP‐ribose)synthetase.
EFFECTS OF GLYCERYL TRINITRATE TOLERANCE ON VASCULAR RESPONSIVENESS TO CONSTRICTOR AGENTS IN BOVINE ISOLATED CORONARY ARTERY
Authors: Zhang C. L. , de la Lande I. S. , Horowitz J. D.
Published: June 2007

1. Recent clinical studies have raised the possibility that intermittent nitrate dose regimens, while limiting the extent of nitrate tolerance development, may trigger rebound aggravation of ischaemia after abrupt withdrawal of nitrate. To date, only limited studies have been performed to examine the mechanism of this phenomenon.

2. In a bovine isolated coronary artery model, we tested the hypothesis that induction of glyceryl trinitrate (GTN) tolerance might affect large coronary artery responsiveness to a variety of non‐catecholamine constrictor agents. Glyceryl trinitrate tolerance was induced by pre‐exposure to GTN (10 μmol/L) for 60 min followed by 15 min washout. In some experiments, the effect of prior endothelial removal on putative interactions was also examined.

3. Our results showed that GTN tolerance did not affect responses to KCI, the thromboxane A2 mimetic U46619, endo‐thelin‐1 and 5‐HT, irrespective of presence or absence of endothelium. None of the constrictor agents tested induced endothelium‐dependent constriction.

4. We conclude that in this model of GTN tolerance induction, there is no evidence of ‘rebound’ vasoconstriction to this group of non‐catecholamine vasoconstrictors with GTN withdrawal.
SPECTRAL ANALYSIS OF SYSTOLIC BLOOD PRESSURE AND HEART RATE OSCILLATIONS RELATED TO RESPIRATION
Authors: Laude Dominique , Weise Frank , Girard Arlette , Elghozi Jean‐Luc
Published: June 2007

1. Non‐invasive assessment of short‐term systolic blood pressure (SBP) and heart rate (HR) variability was obtained with the plethysmographic finger blood pressure measurement device. Respiration was measured with a respiratory inductive plethysmograph, which was calibrated prior to each study.

2. The effects of breathing pattern on the respiratory (high frequency, HF) component of the SBP or HR spectrum were analysed by Fourier transform.

3. Our quantification of the changes in the HF (respiratory) peak of the HR or SBP spectrum with changes in tidal volume (Vt) and breathing frequency (BF) indicates that the modulus of this component may be predicted for any combination of depth and frequency of breathing.

4. The modulus of this HF component for the HR or SBP spectrum was linearly related to the respiratory sinus arrhythmia (RSA) or to the SBP oscillation related to respiration.
ENDOTHELIAL DYSFUNCTION IN CORONARY VESSELS AND THORACIC AORTA OF RATS EXPOSED TO CIGARETTE SMOKE
Authors: Jorge P. A. Ribeiro , Ozaki M. R. , Almeida E. A.
Published: June 2007

1. The aim of this study was to evaluate the role of endothelium in mediating the response to acetylcholine in the thoracic aorta and coronary vessels of rats exposed to cigarette smoking. Total serum cholesterol was measured at the beginning and end of the experiment.

2. The relaxation response to acetylcholine was significantly impaired in the aortae of rats exposed to cigarette smoking (P < 0.05); and the coronary flow during the administration of acetylcholine (0.02 μg/min.) was significantly reduced (P < 0.05). The total cholesterol plasma levels increased 31.13% in those exposed to smoke when compared to the controls (P < 0.05).

3. It is concluded that exposure to cigarette smoking increases total serum cholesterol levels, and also produces primary endothelial dysfunction in aorta rings and coronary vessels.
EFFECTS OF GARLIC EXTRACT ON PLATELET AGGREGATION: A RANDOMIZED PLACEBO‐CONTROLLED DOUBLE‐BLIND STUDY
Authors: Morris Jenny , Burke Valerie , Mori Trevor A. , Vandongen Robert , Beilin Lawrie J.
Published: June 2007

1. Studies of the effects of garlic on platelet aggregation have produced inconsistent results possibly related to variations in study design and in the garlic preparations used.

2. The present study examined the effects on platelet aggregation and serum thromboxane and lyso‐platelet activating factor, of feeding garlic extract to healthy men using a placebo‐controlled, double‐blind design. The effects of the same garlic preparation on platelet aggregation in vitro were also investigated.

3. There were no significant differences in platelet aggregation with adenosine diphosphate, platelet activating factor (PAF) or collagen according to treatment group. Serum thromboxane and IysoPAF also showed no change related to garlic supplements.

4. In vitro aggregation with collagen decreased linearly with increasing amounts of garlic extract, but concentrations were higher than those attainable in vivo. Gastrointestinal side effects prevented the use of higher doses of garlic which must be considered to be pharmacological as they exceed changes achievable by dietary modification.
A CONTROLLED TRIAL OF NURSE COUNSELLING ON LIFESTYLE CHANGE FOR HYPERTENSIVES TREATED IN GENERAL PRACTICE: PRELIMINARY RESULTS
Authors: Woollard J. , Beilin L. , Lord T. , Puddey I. , MacAdam D. , Rouse I.
Published: June 2007

1. We assessed whether a lifestyle modification programme implemented by nurse counsellors in a general practice setting would improve blood pressure (BP) control in treated hypertensive patients.

2. Patients were randomized into a control group or one of two intervention groups who received either a high or low level of counselling.

3. Patients in the intervention groups had appointments every 4th week for 18 weeks. The low intervention group had one practice appointment and five telephone counselling appointments while the high intervention group had six appointments in their general practice. The patients were counselled using a stage of change behavioural model and motivational interviewing to: reduce alcohol consumption, dietary fat and salt intake and weight; cease smoking; and increase leisure time physical activity.

4. Compared with controls the low intervention group showed signifcant decreases in alcohol and salt intake while the high intervention resulted in significant decreases in both weight and BP.

5. We conclude that nurse counselling targeted to specific aspects of lifestyle can improve BP control and weight in treated hypertensive patients over 18 weeks. Its longer term effectiveness in the management of hypertension warrants further evaluation.
SYMPATHETIC REGULATION IN RABBITS WITH HEART FAILURE: EXPERIENCE USING POWER SPECTRAL ANALYSIS OF HEART RATE VARIABILITY
Authors: Moguilevski V. , Oliver J. , McGrath B. P.
Published: June 2007

1. In five intact rabbits β‐adrenoreceptor blockade (i.v. propranolol), and combined cardiac blockade (i.v. propranolol plus i.v. methscopolamine sulphate) revealed that spectral power of heart rate (HR) variability at low frequencies (LF: 0.0625–0.1875 Hz) was modulated predominantly by the sympathetic nervous system and power at high frequencies (HF: 0.4373–0.5625 Hz) by vagal influences.

2. In 16 rabbits resting power of HR at LF and changes in LF power in response to maximal treadmill exercise were examined prior to and after 4 and 6 weeks of doxorubicin treatment (1 mg/kg twice weekly).

3. The development of doxorubicin‐induced congestive heart failure (CHF) was accompanied by a progressive increase in resting LF power [control, 8.5 ± 2.1; 4 weeks, 13.4 ± 1.8; 6 weeks, 21.9 ± 3.5 (beats/min)2, P < 0.005].

4. Power spectral analysis (PSA) of HR variability in the immediate post‐exercise period showed no change from resting values in normal rabbits [5.3 ± 1.4 vs 8.5 ± 2.1 (beats/min)2, P>0.05] whereas CHF rabbits showed falls in LF power after 4 weeks [4.6 ± 1.0 vs 13.4 ± 1.8 (beats/min)2, P < 0.005] and 6 weeks [6.5 ± 2.4 vs 21.9 ± 3.5 (bents/min)2, P < 0.005] of doxorubicin treatment.

5. It was concluded that PSA of HR variability reflects the autonomic regulation of sinus node function in conscious rabbits. In doxorubicin‐treated animals, the rise in LF power reflects increased sympathetic activity as CHF develops. However, the apparent paradoxical fall in LF power with exercise in these animals underscores the need for caution in interpretation of PSA profiles.
INFLUENCE OF BODY TEMPERATURE ON RESPONSES TO HYPOXIA AND HYPERCAPNIA: IMPLICATIONS FOR SIDS
Authors: Maskrey Michael
Published: June 2007

1. This paper reviews current knowledge regarding interactions between body temperature and the respiratory responses to hypoxia and/or hypercapnia, with special emphasis on how these interactions might predispose towards sudden infant death syndrome (SIDS).

2. Use has been made of an adult rat model in which body core temperature is fixed by means of an intra‐abdominal heat exchanger. Initial studies indicated that hyperthermia (Tb∼ 41° C) enhanced the ventilatory response to hypercapnia, whereas hypothermia (Tb∼35°C) interacted with hypoxia to depress respiration.

3. Studies involving hypothalamic lesions in urethane‐anaesthetized rats have implicated the posterior hypothalamic area in the hypoxia/hypothermia interaction. Further studies are directed towards examining the role played by more caudal areas, including the raphe nuclei.

4. It has been shown that not only does the hypoxial hypothermia interaction depress breathing but it also reduces, or sometimes eliminates, the ventilatory response to hypercapnia, which under normal circumstances provides one of the most powerful excitatory inputs to the respiratory centres. This implies that an expected reversal of the respiratory depression by build up of CO2 levels may not occur, which in turn has important implications for SIDS.

5. The literature dealing with the effects of hyperthermia on hypoxic and hypercapnic responses is also reviewed. It is concluded that environmental heat stress may only become a significant problem when it accompanies a febrile infection, under which circumstances it may seriously compromise thermo‐regulatory ability and alter breathing responses to chemical stimuli.
PHYSIOLOGICAL STUDIES OF GASTRO‐OESOPHAGEAL REFLUX AND AIRWAY PROTECTIVE RESPONSES IN THE YOUNG ANIMAL AND HUMAN INFANT
Authors: Jeffery Heather E. , Page Megan , Post Elizabeth J. , Wood Andrew K. W.
Published: June 2007

1. The mechanisms that underlie the Sudden Infant Death Syndrome (SIDS) must explain its two unique features; age at death and death during apparent sleep.

2. The occurrence of gastro‐oesophageal reflux (GOR) during active sleep in infants presenting with apparent life threatening episodes (ALTE) and their similar age distribution to SIDS infants, suggested that reflux could be a cause of asphyxia.

3. Sleep related GOR was found to be a physiological and not a pathological event in normal, healthy term infants.

4. In healthy term infants, those infants that were formula‐fed (who have a higher incidence of SIDS) had significantly longer oesophageal clearance times for acid reflux and significantly more active sleep compared with breast fed infants.

5. In very preterm infants (who are at increased risk for SIDS), both the frequency and duration of reflux during active sleep was significantly less at term equivalent age compared with healthy term infants, suggesting additional factors must operate to promote an ALTE.

6. One mechanism which may explain the pathogenesis of GOR could be that the reflux reaches the level of the pharynx and this, in turn, stimulates laryngeal receptors to produce apnoea.

7. Simulated reflux to the level of the pharynx in the sleeping piglet evoked airway protective responses, namely swallow, arousal and occasionally expectoration, but neither apnoea nor oxygen desaturation.

8. In the same piglets treated with pentobarbitone sodium, swallowing was impaired and arousal depressed. Simulated reflux to the pharynx produced significant apnoea and oxygen desaturation and death in two of five piglets.

9. In the infant, the co‐existence of reflux to the level of the pharynx during sleep, together with impaired swallowing, depressed arousal or both, is one mechanism that may lead to an age‐limited, sudden and fatal apnoea.