bluuebunny/crossref_metadata_2025_split huggingface dataset:
FURTHER EVIDENCE OF THE ROLE OF CYCLIC AMP AS A MEDIATOR OF THE DEPRESSANT EFFECTS OF β‐ADRENOCEPTOR AGONISTS AND PHOSPHODIESTERASE INHIBITORS ON SLOW‐CONTRACTING MAMMALIAN SKELETAL MUSCLES
Authors: Merican Zainuddin , Morat Paden , Dan Rahim , Khalid B. A. K. 
Published: June 2007

SUMMARY1. The depressant effects of β‐adrenoceptor agonists and phosphodiesterase inhibitors on contractions of slow‐contracting mammalian skeletal muscles are associated with increased muscular cyclic AMP levels.2. A strong correlation was found to exist between the percentage depression of contraction and the percentage increase in cyclic AMP level, irrespective of the drug used and regardless of the mechanism of cyclic AMP production.3. The results strongly support the mediatory role of cyclic AMP in the depressant effects of β‐adrenoceptor agonists and phosphodiesterase inhibitors on slow‐contracting mammalian skeletal muscle contractions.
BRAIN NORADRENALINE AND THE DEVELOPMENT OF HYPERTENSION: THE EFFECT OF TREATMENT WITH CENTRAL 6‐HYDROXYDOPAMINE OR DSP‐4
Authors: van den Buuse Maarten , Versteeq Dirk H. G. , de Jong Wybren 
Published: June 2007

SUMMARY1. The relative role of brain catecholamines in the development of hypertension in the spontaneously hypertensive rat (SHR) was studied.2. Treatments consisted in five weeks old SHR of central injections of 6‐hydroxydopamine (6‐OHDA), 3 × 200 μg either intracerebroventricularly (i.c.v.) or intracisternally (i.c.), or of intraperitoneal (i.p.) injections of DSP‐4, either once or three times 50 mg/kg.3. Compared to the pronounced attenuation of the development of hypertension following i.c.v. 6‐OHDA treatment, the i.c. 6‐OHDA treatment and the multiple DSP‐4 treatment were less effective. A single injection of DSP‐4 had only minor effects on blood pressure. Heart rate was markedly lower in i.c.v. 6‐OHDA treated SHR, but the other treatments induced no effects on this parameter.4. Noradrenaline depletion was found in various parts of the brain particularly after i.c.v. 6‐OHDA or either DSP‐4 treatment. Brain dopamine and adrenaline were depleted to a lesser extent. However, the best correlation between blood pressure and brain catecholamine concentration was found for dopamine in the hippocampus and hypothalamus and for adrenaline in the hypothalamus. Noradrenaline levels were also correlated with blood pressure, but to a lesser extent.5. These results suggest that the depletion of dopamine or adrenaline in the brain may be of more importance in the effects of neurotoxic treatments on the development of hypertension than the effects on brain noradrenaline. Thus, these experiments lend support to the hypothesis that brain noradrenaline systems may not play an important role in the development of hypertension in the SHR.
RELATION OF INTRAMYOCARDIAL PRESSURE TO CORONARY PRESSURE AT ZERO FLOW
Authors: Sabbah Hani N. , Marzilli Mario , Liu Zhi‐quan , Stein Paul D. 
Published: June 2007

SUMMARY1. The purpose of this study was to determine the extent to which coronary pressure at zero coronary flow (Pf=0) may relate to extravascular compressive forces determined by direct measurements of left ventricular intramyocardial pressure.2. Studies were performed in nine open‐chest anaesthetized dogs in which the anterior descending coronary artery was cannulated and perfused from the carotid artery. Coronary pressure was measured at the tip of the cannula.3. Intramyocardial pressure was measured with a 1 mm diameter micromanometer inserted directly into the subepicardium. The atrioventricular node was obliterated by cautery and the heart was electrically paced. Long diastolic pauses, sufficient to allow coronary flow to reach zero, were produced by the cessation of electrical pacing.4. In the autoregulated coronary bed, Pf=0, 47 mmHg (s.e.m. = 9), exceeded subepicardial pressure at zero flow, 23 mmHg (s.e.m. =2; P < 0.001). During maximal vasodilatation with adenosine, Pf=0, 16 mmHg (s.e.m. = 11), was not significantly different from subepicardial pressure at zero flow, 21 mmHg (s.e.m. =4). These observations indicate that, in addition to coronary vasomotor tone, diastolic myocardial tissue pressure is important in the genesis of Pf=0.
EFFECTS OF A SYNTHESIZED PHOSPHODIESTERASE INHIBITOR, ZSY‐27, ON PANCREATIC EXOCRINE SECRETION OF THE DOG
Authors: Iwatsuki K. , Yamagishi F. , Chiba S. 
Published: June 2007

SUMMARY1. The effects of a synthesized phosphodiesterase inhibitor, ZSY‐27, on the secretion of pancreatic juice were investigated in dog isolated and blood‐perfused pancreas, and compared with those of secretin and dopamine.2. Intravenous administration of ZSY‐27 (0.3‐1 mg/kg) elicited increases in pancreatic secretion. Intra‐arterial (i.a.) administration of ZSY‐27 (0.1‐1 mg) also elicited increased secretion. The secretory activity of ZSY‐27 (1 mg) was approximately equal to that of 0.1 units of secretin and 2.5 μg of dopamine.3. The concentration of bicarbonate in the pancreatic juice induced by ZSY‐27 i.a. was increased, but the protein concentration was not increased significantly. These effects are analogous to those of secretin and dopamine.4. ZSY‐27‐induced pancreatic secretion was not modified by pretreatment with phentolamine, propranolol, atropine, sulpiride and cimetidine.5. Secretin‐induced secretion was significantly potentiated by infusion of ZSY‐27 (25 μg/min) but dopamine‐induced one was not.6. These results suggest that ZSY‐27 increases pancreatic secretion acting directly on the ductular cells of the dog pancreas, at least in part, through the increase of intra‐cellular cyclic AMP concentration by inhibiting phosphodiesterase activity.
BAROREFLEX SENSITIVITY ALTERATION FOLLOWING TRANSIENT HEMISPHERIC ISCHAEMIA IN RATS: PROTECTIVE EFFECT OF ALPHAMETHYLDOPA AND GUANFACINE
Authors: Saad Mohamed A. A. , Elghozi Jean‐Luc , Meyer Philippe 
Published: June 2007

SUMMARY1. The reflex tachycardia to arterial vasodilation was analysed in anaesthetized and ventilated Long Evans rats. Nicardipine was given by slow intravenous injection. The decrease in blood pressure was accompanied by a sympathetically mediated reflex tachycardia. The slope of the mean blood pressure‐pulse period relationship was considered as an index of baroreflex sensitivity. Two injections of nicardipine were given during a single experiment.2. For studying the suprapontine control of the baroreflex arc, rats were subjected to transient (10 min) bilateral hemispheric ischaemia. These rats exhibited a blood pressure drop following recirculation and baroreflex sensitivity was impaired.3. Pretreatment with α‐methyldopa, guanfacine and enalapril lowered mean blood pressure to a similar extent. In those rats pretreated with α‐methyldopa and guanfacine transient hemispheric ischaemia did not alter baroreflex sensitivity while enalapril pretreated rats exhibited an impaired baroreflex. The protective effect of α‐methyldopa and guanfacine against the cardiovascular consequence of hemispheric ischaemia may depend on reduced monoamine turnover resulting from central α‐adrenoceptor stimulation.
PRESSOR SENSITIVITY TO ANGIOTENSIN I AND ANGIOTENSIN II DURING THE DEVELOPMENT OF EXPERIMENTAL RENAL HYPERTENSION IN THE RAT
Authors: Doyle A. E. , Harrap S. B. , Torresi J. 
Published: June 2007

SUMMARY1. Treatment with the potent angiotensin converting enzyme inhibitor perindopril completely prevented any rise in blood pressure in the 2‐kidney, 1 ‐clip (2K1C) model of renal hypertension in rats. Withdrawal of this inhibitor was followed by a slow rise in blood pressure.2. In 2K1C rats treated with perindopril, pressor responses to angiotensin I fell during the treatment period, but returned to normal after the inhibitor was stopped. Pressor responses to angiotensin II (AII) increased during treatment with perindopril; this was presumably due to increased receptor sensitivity consequent on the falls in endogenous AII levels. Responses to AII fell to control levels after the inhibitor was stopped.3. It is concluded that an increased pressor sensitivity to AII is not the cause of the slowly developing hypertension in the 2K1C model of hypertension, and that the slow pressor response to AII must be due to other factors.
RENAL PROSTAGLANDIN EFFLUX INDUCED BY VASOPRESSIN, DDAVP AND ARACHIDONIC ACID: CONTRASTING PROFILE AND SITES OF RELEASE
Authors: Miller Mark J. S. , Westlin William F. , McNeill Helen , McGiff John C. 
Published: June 2007

SUMMARY1. Prostaglandin (PG) efflux into ureteral (UE) and venous effluents (VE) of rabbit isolated perfused kidneys was determined by superfusion bioassay and radioimmunoassay (RIA), in response to injections of arginine‐vasopressin (AVP), the non‐pressor vasopressin analogue 1‐deamino‐8‐D‐arginine vasopressin (dDAVP) and arachidonic acid (AA).2. dDAVP (10–1000 ng) failed to stimulate renal PG release, whereas AVP (10–100 ng) and AA (10–50 μg) caused a dose‐dependent release of PG.3. AVP evoked PG release into both effluents with release into the VE greater than UE at high doses. In contrast, PG release by AA was almost exclusively into the VE.4. Indomethacin (2.8 × 10‐6 mol/1) abolished AVP‐ and AA‐induced PG efflux in both effluents, and vasodepressor responses to AA.5. PGE2 was the predominant PG released in response to AVP in both effluents whereas AA released primarily 6‐keto‐PGF1α.6. The contrasting sites and profile of released PG suggest that exogenous AA and AVP stimulate the release of PG from different regions/cell types within the kidney.
PROSTANOID CONCENTRATIONS IN HUMAN CSF FOLLOWING ACUTE ISCHAEMIC BRAIN INFARCTION
Authors: Fagan S. C. , Castellani D. , Gengo F. M. 
Published: June 2007

SUMMARY1. Thromboxane A2 and prostacyclin are two compounds which have been implicated as important modulators of local cerebral blood flow.2. Concentrations of the stable metabolites of these two compounds, thromboxane B2 and 6‐keto‐PGF1α, were measured in cerebrospinal fluid (CSF) from eight acute ischaemic stroke patients and 14 patients with no evidence of cerebrovascular disease.3. Concentrations of thromboxane B2 ranged from 0.15 to 4.0 pg/ml and were significantly higher (P= 0.025) in the ischaemic stroke group when compared with the control group (0.1–0.3 pg/ml). Simultaneously acquired concentrations of 6‐keto‐PGF1α were not elevated in the stroke group when compared to normals.4. These clinical findings support evidence from animal studies that emphasizes the importance of cerebral prostaglandins in mediating the secondary vascular changes of cerebral infarction. In conclusion there is an aberration in CSF thromboxane B2 concentrations in patients who have had a stroke. This may be an acute or chronic phenomenon.
PROPRANOLOL AMELIORATES EXERCISE‐INDUCED REGIONAL MYOCARDIAL DYSFUNCTION IN DOGS
Authors: Mayer N. , Krumpl G. , Schneider W. , Raberger G. 
Published: June 2007

SUMMARY1. The effects of propranolol (0.5 mg/kg) on exercise‐induced regional myocardial dysfunction were investigated in an animal model with limited coronary reserve.2. Limited coronary reserve was accomplished in conscious, chronically instrumented dogs by external filling of a hydraulic cuff occluder placed on a coronary vessel which did not impair resting myocardial function but induced severe dysfunction during treadmill exercise.3. Propranolol led to a distinct reduction of heart rate, myocardial contractility and systolic blood pressure, thereby ameliorating exercise‐induced regional myocardial dysfunction.
THE EFFECT OF HIGH FREQUENCY OSCILLATORY VENTILATION ON EXTRAVASCULAR LUNG WATER IN THE RABBIT
Authors: Ritchie B. C. , Brodecky V. , Scott A. , Wilkinson M. H. 
Published: June 2007

SUMMARY1. High frequency ventilation (HFV) systems have the theoretical advantage of producing less barotrauma and lung damage because of the associated smaller oscillations in alveolar pressure compared to conventional ventilators.2. An index of lung damage is an increase in extravascular lung water but previous studies using HFV have produced conflicting results.3. Lung wet‐to‐dry ratio, extravascular lung water and blood mass were measured in 30 rabbits divided into three groups (n= 10); spontaneously breathing (SV), conventional positive pressure ventilation (CV) and high frequency oscillatory ventilation (HFV).4. HFV maintained normal blood gases and produced a significant reduction in the wet‐to‐dry weight ratio compared to SV and CV (P < 0.05). Extravascular lung water and blood mass were significantly reduced in HFV compared to SV (P < 0.05).5. It is concluded that the system of HFV used in this study has clinical potential in the treatment of lung injury.
STREPTOKINASE ALTERS MYOCARDIAL CREATINE KINASE DEPLETION AFTER ISCHAEMIA AND REPERFUSION IN RABBITS
Authors: Mickelson J. K. , Carlson C. J. , Margaretten W. , Rapaport E. 
Published: June 2007

SUMMARY1. The efficacy of streptokinase as an intracoronary thrombolytic agent is wellrecognized. The effect of streptokinase, distinct from its thrombolytic action, on ischaemic myocardium distal to an area of coronary artery occlusion when reperfusion occurs has not been well‐defined.2. In order to do this, myocardial creatine kinase depletion and the histopathology of infarctions produced in rabbits after 1 h of circumflex coronary artery occlusion and mechanical release of the occlusion were assessed.3. Streptokinase or saline was infused intravenously for 1 h beginning 0.5 h after occlusion. Rabbits were divided into two time intervals: early (<10 h) and late (24 h) after release of coronary artery occlusion.4. When streptokinase was infused in early infarctions, haemorrhage did not correlate with infarction cross‐sectional area or myocardial creatine kinase depletion. However, myocardial creatine kinase depletion was 40% less when streptokinase was infused than when saline was infused, suggesting that streptokinase might limit infarct size.5. In late infarctions, the degree of haemorrhage, infarction cross‐sectional area, and myocardial creatine kinase depletion were similar after reperfusion with streptokinase or saline. By 24 h, the beneficial effect of a single dose of streptokinase given early in the course of occlusion‐reperfusion myocardial injury was no longer evident in limiting infarct size.
NUCLEAR LOCALIZATION OF TYPE 1 ALDOSTERONE BINDING SITES IN STEROID‐UNEXPOSED GH3 CELLS
Authors: Pearce Paul T. , McNally Margaret , Funder John W. 
Published: June 2007

SUMMARY1. The nuclear localization of unoccupied oestrogen receptors has been demonstrated in MCF 7 (human breast tumour) cells by immunocytochemistry, and in GH3 (rat pituitary tumour) cells by enucleation techniques.2. The present study shows, by similar enucleation techniques, that high affinity (Type 1) aldosterone binding sites are similarly located in the nucleus of steroidunexposed pituitary GH3 cells.3. It is, therefore, suggested that such high‐affinity Type 1 sites, which are mineralocorticoid receptors in the kidney and glucocorticoid receptors in the hippocampus, are nuclear‐associated proteins in the absence of steroid and are found in the cytosol compartment only upon cell disruption.
ACCELERATED PROGRESSION OF DIABETIC NEPHROPATHY IN THE SPONTANEOUSLY HYPERTENSIVE STREPTOZOTOCIN DIABETIC RAT
Authors: Cooper M. E. , Allen T. J. , Jerums G. , Doyle A. E. 
Published: June 2007

SUMMARY1. Streptozotocin (STZ)‐diabetes was induced in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats with their litter mates serving as controls. The animals were studied for 6 months and blood pressure, weight, urinary and serum glucose, creatinine clearance, total proteinuria and albuminuria were measured monthly.2. With induction of diabetes, there was a significant rise in creatinine clearance in the hypertensive diabetic animals (SHR‐STZ). SHR‐STZ (n= 6) developed higher levels of total proteinuria than WKY‐STZ (n= 5) although the rise from basal levels was only apparent after 20 weeks of diabetes. All SHR‐STZ developed albustix positive proteinuria after 6 months of diabetes.3. In the first 12 weeks after onset of diabetes, albuminuria increased to a greater degree in SHR‐STZ than in WKY‐STZ. This occurred before there was a detectable rise in total proteinuria.4. The SHR‐STZ model of genetic hypertension and diabetes may be suitable for the evaluation of antihypertensive therapy in human diabetic renal disease.
CHARACTERIZATION OF ANGIOTENSIN CONVERTING ENZYME FROM RAT TISSUE BY RADIO‐INHIBITOR BINDING STUDIES
Authors: Jackson Bruce , Cubela Rose , Johnston Colin I. 
Published: June 2007

SUMMARY1. Angiotensin converting enzyme (ACE) derived from rat lung, aorta, epididymus, brain, kidney and plasma was characterized by radio‐inhibitor (125I‐MK351A) binding studies. Under optimal binding conditions at equilibrium 125I‐MK351A bound to ACE was displaced from ACE in a concentration related manner by unlabelled MK351A.2. MK351A binding site concentration for each tissue and equilibrium dissociation constant (KD) was estimated by Scatchard analysis of binding data. Binding sites/mg protein was greatest in lung and least in brain. The KD for kidney ACE was significantly higher than that of lung, aorta, epididymus or brain ACE (P<0.005; t‐test, d.f. = 10).3. 125I‐MK351A bound to ACE prepared from lung and kidney was displaced in a concentration dependent manner by SQ20881, SQ14225, MK422, and Ro31–3113–000. Concentration of ACE inhibitor required to displace 50% of bound 125I‐MK351A (DD50) was consistently higher for kidney‐derived ACE than lung‐derived ACE.4. The differences in radio‐inhibitor binding characteristics of ACE from different rat tissues suggests that the enzyme active site may not be identical in all organs.
EFFECTS OF ARACHIDONATE DEFICIENCY ON ENDOTHELIUM‐ DEPENDENT VASCULAR REACTIONS
Authors: Loiacono R. E. , Kudo K. , Dusting G. J. , Sinclair A. J. 
Published: June 2007

SUMMARY1. The release of endothelium‐derived relaxing factor (EDRF), which appears to be impaired in vessels chronically exposed to hypertension, may involve mobilization of arachidonate from phospholipids. In this study the effects of arachidonate deficiency on endothelium‐dependent responses were examined in rat isolated aorta.2. Weanling rats were fed an essential fatty acid‐deficient (EFAD) diet for 8 weeks which reduced plasma and aortic phospholipid arachidonate content from 17 to 1.8% and from 21 to 8%, respectively. After this time the rats were killed and the reactivity of aortic rings was studied in organ baths.3. In aortic rings from control rats the concentration‐response curves for the contractile action of phenylephrine were shifted to the left 3.5‐fold by removal of the endothelium, and the maximum was not altered.4. In contrast, in EFAD rings with endothelium, the maximal vasoconstriction to phenylephrine was less than in control rings, and removal of the endothelium increased the maximum (from 1.9±0.2 to 3.2±0.1 g, P < 0.05) and reduced the EC50 7‐fold.5. In EFAD rings precontracted with phenylephrine (0.3 μml/l) the relaxations produced by the endothelium‐dependent dilator acetylcholine were not significantly different from those produced in control rings. The dilator actions of sodium nitroprusside were also similar in EFAD and control rings.6. Thus, endothelium‐dependent dilatation in the aorta is not impaired by partial depletion of phospholipid arachidonate. However, contractile responses to α‐adrenoceptor agonists are depressed by spontaneously released EDRF in rat aorta, so that the results suggest that depletion of phospholipid arachidonate either augments spontaneous release of EDRF, or impairs EDRF inactivating mechanisms.
RELATIONSHIP BETWEEN PLATELET CYTOSOLIC FREE CALCIUM CONCENTRATION AND PLASMA RENIN ACTIVITY
Authors: Sang Kim Hahn Le Quan , Elghozi Jean‐Luc , Meyer Philippe , Devynck Marie‐Aude 
Published: June 2007

SUMMARY1. Plasma renin activity (PRA) and platelet cytosolic free calcium concentration ([Ca2+]i) were simultaneously determined in 18 untreated essential hypertensive subjects and 17 normotensive controls. A significant positive correlation was found between [Ca2+]i and PRA (slope = 42 nmol/l/ng/ml/h) in these 35 subjects.2. Two determinations more than one week apart in nine subjects confirmed the parallel fluctuations of [Ca2+]i and PRA. A strict sodium restriction produced a progressive PRA elevation associated with a parallel rise in [Ca2+]i in one subject.3. These results are consistent with the hypothesis that angiotensin II causes a concentration‐dependent calcium mobilization.
STUDY OF RECEPTOR‐STIMULATED PHOSPHATIDYLINOSITOL HYDROLYSIS IN INTACT, PERFUSED RAT HEARTS
Authors: Woodcock Elizabeth A. , McLeod Jennifer K. , Smith A. Ian , Clark Michael G. 
Published: June 2007

SUMMARY1. Phosphatidylinositol turnover has been measured in intact, perfused rat hearts by measuring generation of inositol phosphates following [3H]‐inositol labelling. Stimulation of accumulations of inositol wonophosphate, inositol bisphosphate and inositol tris phosphate were observed during perfusion with either noradrenaline (3×10‐5 mol/l) or carbachol (10‐3 mol/l).2. Stimulation by noradrenaline was antagonized by prazosin (10‐7 mol/l) but not by propranolol (10‐7 mol/l), indicating mediation via α‐adrenoceptors. Stimulation by carbachol was antagonized by atropine (10‐7 mol/l).3. Transmural electrical stimulation of the hearts failed to increase inositol phosphate accumulation through α1‐adrenoceptors. A small stimulation mediated by muscarinic receptors was observed. Therefore α1‐adrenoceptors which stimulate phosphatidylinositol turnover probably do not have a synaptic localization in heart.4. The development of methods for the study of phosphatidylinositol turnover in intact hearts will facilitate an investigation of relationships between this signal transduction pathway and cardiac function.
HANDLING OF A SODIUM LOAD BY RATS ON A LOW SODIUM INTAKE AND FRUSEMIDE
Authors: Ledingham Janet M. , Simpson F. O. 
Published: June 2007

SUMMARY1. Groups of rats (n= 9–10 per group) were given a medium sodium (Na) diet or a low Na diet or a low Na diet plus low or high dose frusemide in order to have their body Na in a state of surplus or deficit or neither.2. Body Na was measured by a 22Na whole body counting method involving Na‐free chow and the drinking fluid as the only source of Na (22Na‐labelled NaCl). Intraperitoneal NaCl (same specific activity) loads were given and their excretion was measured by repeated measurements of body Na over the next 48 h.3. Rats in surplus excreted more than the load; those in neither surplus nor deficit excreted more or less exactly the load (allowing for growth); those with a small deficit retained enough Na to make up most of the deficit; those with a deficit that was larger than the load retained approximately the whole load.4. The results support the Strauss‐Hollenberg concept that there is a basal body Na above which Na is excreted and below which any available Na is retained.
ANGIOTENSIN II‐INDUCED CONTRACTION OF MESANGIAL CELLS IN ACUTE RENAL ARTERY STENOSIS IN DOGS
Authors: Anderson W. P. , Alcorn D. , Gilchrist A. I. , Ryan G. B. 
Published: June 2007

SUMMARY1. Renal artery stenosis was induced in anaesthetized dogs, and the kidney rapidly fixed after 30 min.2. Electron microscopy revealed marked folding of the paramesangial basement membrane in stenotic kidneys (n= 7). The extent of this folding was significantly less in dogs treated with captopril (n= 6).3. It is suggested that this folding reflects angiotensin II‐induced contraction of the mesangial cells, which may help maintain glomerular filtration rate following stenosis.