bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperglycaemia: A Morphine‐Like Effect Produced By Naloxone
Authors: Abouazra Ha , Sharif Si 
Published: March 2003

SUMMARY1. Naloxone, which is often regarded as a pure opioid antagonist, produces effects similar to those produced by morphine.2. In conscious rabbits implanted with an intracerebroventricular (i.c.v.) cannula, naloxone, whether given intravenously (1 mg/kg) or i.c.v. (1–100 μg), produced a significant rise in blood glucose levels.3. Hyperglycaemia in response to naloxone (1 mg/kg, i.v., or 100 μg, i.c.v.) was not influenced by the selective α1‐adrenoceptor antagonist WB‐4101 given either i.v. (50 μg) or i.c.v. (5 μg).4. Hyperglycaemia in response to naloxone (1 mg/kg, i.v., or 100 μg, i.c.v.) was completely blocked by pretreatment with the α2‐adrenoceptor antagonist yohimbine (1 mg/kg, i.v., or 100 μg, i.c.v.). However, hyperglycaemia to i.c.v. naloxone (100 μg) was not influenced by i.v. yohimbine (1 mg/kg).5. Because naloxone behaves like morphine and produces hyperglycaemia in conscious rabbits, the drug may have an appreciable agonist activity and the hyperglycaemic response to naloxone is principally mediated via α2‐ but not α1‐adrenoceptors.
Allosteric Modulation of the GabaA Receptor In Rat Hypothalamus By Somatostatin Is Altered By Stress
Authors: Chigr F , M'Hamed S Ba , Najimi M 
Published: March 2003

SUMMARY1. This autoradiographic study was conducted to investigate somatostatin modulation of GABAA receptor binding in hypothalamic structures of immobilization‐stressed rats.2. GABAA receptor binding was labelled with [35S]‐t‐ butylbicyclophosphorothionate (TBPS), which binds in or near the chloride channel.3. Several structures of the rat hypothalamus (i.e. the peri‐ and paraventricular nuclei) display an increase in [35S]‐TBPS binding as well as an alteration of the modulatory effect of somatostatin on the GABAA receptor complex under stress. Furthermore, these results demonstrate for the first time that somatostatin is particularly effective in modifying [35S]‐TBPS binding to the GABAA receptor in rat hypothalamus.
Extracellular ATP and cAMP as Paracrine and Interorgan Regulators of Renal Function Renal Microvascular Effects of P2 Receptor Stimulation
Authors: Inscho Edward W 
Published: March 2003

SUMMARY1. The field of extracellular nucleotides and purinoceptors has undergone a resurgence of interest and enthusiasm in the past decade. More and more investigators are probing the physiological and pathophysiological roles of P2 receptors in virtually every organ system, including the kidney.2. With this renewed interest has come a new appreciation for the roles extracellular adenine nucleotides can play in regulating or modulating renal function. In the past 5 years, investigators have provided compelling evidence that extracellular nucleotides, working through activation of P2 purinoceptors, have a significant impact on renal microvascular function, mesangial cell function and on renal epithelial transport.3. Evidence has been uncovered that implicates P2 receptor activation in mediating renal microvascular autoregulatory behaviour. Locally released ATP has a direct paracrine and/or autocrine effect modulating renal epithelial transporters and tubular epithelial channels to influence tubular fluid composition.4. While the specific roles of extracellular nucleotides and their receptors in the kidney have not been absolutely identified, it now appears clear that endogenously released ATP may play a significant role in regulating kidney function.5. The purpose of the present review is to update our current understanding of the effect of P2 receptor activation on renal microvascular function and to detail the signal transduction mechanisms known to be involved.
Significance Of Exaggerated Natriuresis After Angiotensin AT1 Receptor Blockade Or Angiotensin‐ Converting Enzyme Inhibition In Obese Zucker Rats
Authors: Tallam Lakshmi S , Jandhyala Bhagavan S 
Published: March 2003

SUMMARY1. Obese Zucker rats (OZR) were shown to be salt‐sensitive in that they develop hypertension when placed on a high‐salt diet. Because angiotensin (Ang) II is a major antinatriuretic factor, the present studies were undertaken to determine whether the characteristic of salt‐sensitivity of OZR is associated with an enhanced antinatriuretic function of endogenous AngII.2. The extent of AngII‐mediated antinatriuresis was investigated in OZR and lean Zucker rats (LZR) using candesartan (100 μg/kg, i.v.), a selective angiotensin AT1 receptor antagonist, and ramipril (1 mg/kg, i.v.), an angiotensin‐converting enzyme (ACE) inhibitor. The total number of AngII binding sites and their affinity were also assessed in renal cortical tubular membrane preparations of OZR and LZR using a specific radioligand‐binding assay. Plasma renin activity was determined using a standard radioimmunoassay.3. Both candesartan and ramipril produced substantially greater increases in urinary sodium excretion and urine flow in OZR and these effects were significantly greater than those observed in LZR. These observations suggest that basal antinatriuretic function of endogenous AngII is exaggerated in OZR.4. The functional overexpression of AngII was not due to any alterations in the affinity or the total number of AngII binding sites in renal cortical tubular membranes. Higher plasma renin values in the OZR could have contributed to the phenomenon.5. In conclusion, marked diuresis and natriuresis after AT1 receptor blockade and/or ACE inhibition suggest that the extent of endogenous AngII‐mediated sodium transport under basal conditions is greatly augmented in OZR. It is proposed this phenomenon may be a contributing factor for the salt‐ sensitivity in the OZR.
Co‐Release Of Endogenous ATP And Noradrenaline From Guinea‐Pig Mesenteric Veins Exceeds Co‐Release From Mesenteric Arteries
Authors: Bobalova Janette , Mutafova‐Yambolieva Violeta N 
Published: March 2003

SUMMARY1. The present study was designed to compare the overflow of sympathetic neurotransmitters of guinea‐pig inferior mesenteric artery and mesenteric vein evoked by electrical field stimulation (EFS) with special emphasis on the simultaneous release of ATP and noradrenaline (NA). The stimulation‐evoked overflow of ADP, AMP and adenosine was also evaluated.2. Endothelium‐denuded segments of inferior mesenteric arteries or veins were superfused in a small volume (200μL)‐chamber for EFS and subsequent detection of NA (HPLC– electrochemical detection) and adenine nucleotides and adenosine (HPLC–fluorescence detection) in samples of the superfusate.3. Both arteries and veins responded to EFS (15 V, 4–16 Hz, 0.3 msec for 60 s) with overflow of ATP and NA in a tetrodotoxin (1μmol/L)‐ and guanethidine (10μmol/L)‐sensitive manner. The EFS‐evoked overflow of NA in veins exceeded the overflow of NA in arteries at all frequencies of stimulation, whereas the EFS‐evoked overflow of ATP, ADP and AMP in veins exceeded the overflow of adenine nucleotides in arteries at 4 and 8 Hz but not at 16 Hz stimulation. The EFS–evoked overflow of adenosine was similar in arteries and veins.4. Activation ofα1‐adrenoceptors with methoxamine (10μmol/L) did not produce overflow of ATP.5. Blockade ofα1/α2‐adrenoceptors with phentolamine (1μmol/L) did not affect EFS‐evoked overflow of ATP, ADP, AMP and adenosine.6. It is concluded that overflow of ATP and NA from sympathetic nerves may constitute an effective mechanism in the complex balance between capacitance and resistance in splanchnic circulation.
John Ludbrook APPS Symposium Coronary–Bronchial Blood Flow And Airway Dimensions In Exercise‐Induced Syndromes
Authors: White Sw , Pitsillides Kf , Parsons Gh , Hayes Sg , Gunther Ra , Cottee Db 
Published: March 2003

SUMMARY1. We have an incomplete understanding of integrative cardiopulmonary control during exercise and particularly during the postexercise period, when symptoms and signs of myocardial ischaemia and exercise‐induced asthma not present during exercise may appear.2. The hypothesis is advanced that baroreflex de‐resetting during exercise recovery is normally associated with (i) a dominant sympathetic vasoconstrictor effect in the coronary circulation, which, when associated with obstructive coronary disease, may initiate a potentially positive‐feedback cardio‐ cardiac sympathetic reflex (variable myocardial ischaemia with symptoms and signs); and (ii) a dominant parasympathetic bronchoconstrictor effect in the presence of bronchovascular dilatation, which, when associated with raised mediator release in the bronchial wall, reinforces the tendency for airway obstruction (variable dyspnoea results).3. There is a need for new techniques to examine hypotheses concerning autonomic control, during and after exercise, of the coronary and bronchial circulations and the dimensions of airways. Accordingly, a new ultrasonic instrument has been designed named an ‘Airways Internal Diameter Assessment (AIDA) Sonomicrometer’. It combines pulsed Doppler flowmetry with transit‐time sonomicrometry of airway circumference and single‐crystal sonomicrometry of airway wall thickness. Initial evaluation suggests it is relatively easy to apply during thoracotomy in recovery animals. The component devices are linear and will measure target variables with excellent accuracy.4. In anaesthetized sheep, intubated with controlled ventilation, intravenous isoproterenol causes large increases in bronchial blood flow, a fall in arterial pressure and a reduction in airway circumference. This may reflect the dominant action of reflex vagal activity over direct β‐adrenoceptor inhibition of bronchial smooth muscle, the reflex source being baroreflex secondary to the fall in arterial pressure. These findings provide insight into the integrative mechanisms underlying the paradoxical negative effects sometimes observed when β‐adrenoceptor agonists are used in asthma.
Pirfenidone Inhibits Dimethylnitrosamine‐Induced Hepatic Fibrosis In Rats
Authors: Tada Seiya , Nakamuta Makoto , Enjoji Munechika , Sugimoto Rie , Iwamoto Hiroaki , Kato Masaki , Nakashima Yutaka , Nawata Hajime 
Published: March 2003

SUMMARY1. In the present study, we investigated the preventive effects of pirfenidone (PFD), an antifibrotic agent, on experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats.2. Treatment with DMN caused a significant decrease in bodyweight and liver weight. Oral PFD (500 mg/kg daily for 4 weeks) essentially prevented this DMN‐induced loss in bodyweight and tended to suppress the loss in liver weight. There were no significant differences in liver weight and serum L‐alanine aminotransferase levels between PFD‐treated and ‐untreated groups. Pirfenidone has no major side effects in vivo.3. Pirfenidone suppressed the induction of hepatic fibrosis determined by histological evaluation and reduced hepatic hydroxyproline levels. Expression of mRNA for type I collagen and transforming growth facter‐β in the liver was also suppressed by PFD treatment.4. Because hepatic stellate cells (HSC) are the major cellular source of extracellular matrix in hepatic fibrosis, we examined the effects of PFD on type I collagen production in vitro using rat primary HSC cultures. Pirfenidone inhibited collagen production in HSC culture in a dose‐dependent manner.5. These results demonstrate that the inhibitory effects of PFD against hepatic fibrosis may be due, at least in part, to blockade of collagen production by HSC and suggest that PFD may be potentially useful in the prevention of the development of hepatic fibrosis.
Exacerbatory mechanism responsible for water immersion stress‐induced gastric lesions in aged rats compared with young rats
Authors: Goto Hidemi , Tachi Kosuke , Hisanaga Yasuhiro , Kamiya Kenji , Ohmiya Naoki , Niwa Yasumasa , Hayakawa Tetsuo 
Published: March 2003

SUMMARY1. The present study was designed to investigate whether or not ageing affects the development of water immersion stress‐induced gastric lesions in rats. Effects of cetraxate, an anti‐ulcer drug, were also examined.2. Gastric lesions were induced by 6 h water immersion stress in rats. Gastric mucosal blood flow was determined by the hydrogen gas clearance technique and nitric oxide synthase (NOS) activity was measured enzymatically.3. Early development of gastric lesions was observed in aged rats and exacerbation of gastric lesions was also found. Lowering of gastric mucosal blood flow and reduced NOS activity were observed in aged rats.4. Cetraxate mitigated the development of gastric lesions in young rats and also increased gastric mucosal blood flow and NOS activity. However, these favourable effects were diminished in aged rats.5. Decreased NOS activity may be an important exacerbatory factor to the development of gastric lesions in aged rats.6. Effects of cetraxate differed between young rats and aged rats.7. These results may explain the refractoriness and drug resistance in gastric ulcers encountered by elderly individuals.
Hypervolaemia improves global and local function and efficiency in postischaemic myocardium
Authors: Du FY , Chen X‐L , Drzewiecki G , Li JK‐J , Kedem J 
Published: March 2003

SUMMARY1. In the present study, we investigated the effects of blood volume on postischaemic function and efficiency. In 14 anaesthetized dogs, following recovery from a period of 15 min occlusion of the left anterior descending coronary artery, the effects of hypervolaemia (HYPER; 15% increased volume produced by fast infusion of Hespan; B Braun Medical, Irvine, CA, USA), normovolaemia (NORMO) and hypovolaemia (HYPO) were studied.2. Although myocardial O2 consumption was not significantly increased by volume (6.37±0.94 vs 6.89±1.1 mL/min per 100 g for HYPO and HYPER, respectively), local work of the stunned myocardium was markedly elevated (8.8±1.7 vs 22.5±3.5 g·mm/ beat, for HYPO and HYPER, respectively; P < 0.05). External work of the heart was also significantly improved (71.8±12.7 vs 139.5±16.2 mmHg·L/min for HYPO and HYPER, respectively). These data indicate markedly improved efficiency produced by volume, because work was increased with no change in myocardial O2 consumption.3. Local dysfunction was characterized by several parameters, including systolic bulge, end‐diastolic length, delay to onset of shortening, end shortening time delay (EST) and tail work ratio. Hypervolaemia reduced EST compared with hypovolaemia (98.6±18.3 vs 110.7±14.9 msec, respectively; P < 0.05) and improved tail work ratio (28.0±7.0 vs 36.0±7.0%, respectively; P < 0.05), with no effects on systolic bulge, end‐diastolic length and delay to onset of shortening.4. Thus, even in the postischaemic myocardium, increasing work by volume is energetically efficient and is accompanied by partial improvement of local dysfunction.
Telemetric Monitoring Of Adrenocorticotrophin‐Induced Hypertension In Mice
Authors: Schyvens CG , Mangos GJ , Zhang Y , McKenzie KUS , Whitworth JA 
Published: March 2003

SUMMARY1. The mouse is the animal of choice for studies involving genetic manipulation and transgenic and knockout mice are valuable tools for physiological studies. We have studied adrenocorticotrophin (ACTH)‐ and steroid‐induced hypertension in both rat and humans. The aim of the present study was to develop a model of ACTH‐induced hypertension in the mouse and to assess a chronically implanted telemetric device for measurement of blood pressure (BP).2. Male Swiss Outbred and Quackenbush Swiss (QS) mice (35–45 g) were implanted with TA11PA‐C20 BP devices (Data Sciences International, St Paul, MN, USA) under isoflurane anaesthesia. Seven to 10 days later, mice were monitored telemetrically for baseline BP for 4 days. Mice were then randomly allocated to: (i) sham treatment with normal saline s.c.; or (ii) ACTH at 500 μg/kg per day, s.c. Mice were monitored 24 h/day for 10 days.3. Sham treatment (n = 7) did not affect BP (114 ± 2/84 ± 1 to 115 ± 2/84 ± 1 mmHg; P = NS). Adrenocorticotrophin treatment (n = 5) raised BP from 112 ± 7/82 ± 4 to 138 ± 3/104 ± 4 mmHg, which was significantly different from sham treatment (P = 0.0021 for systolic BP; P < 0.0001 diastolic BP). The increase in BP with ACTH was comparable with that seen in previous studies in humans, sheep and rat. Sham and ACTH‐treated animals each lost 3% bodyweight.4. Administration of ACTH (500 μg/kg per day) raises BP in two strains of mice, measured using a telemetry system. This model will allow the selective use of transgenic and/or knockout mice to further elucidate the mechanism of ACTH‐ and steroid–induced hypertension.
Elevated Serum Endogenous Inhibitor Of Nitric Oxide Synthase And Endothelial Dysfunction In Aged Rats
Authors: Xiong Yan , Yuan Li‐Wei , Deng Hang‐Wu , Li Yuan‐Jian , Chen Ben‐Mei 
Published: March 2003

SUMMARY1. The purpose of the present study was to determine the relationship between endothelial dysfunction and the endogenous inhibitor of nitric oxide synthase NG,NG′‐asymmetric dimethylarginine (ADMA) in aged rats.2. Studies were performed in male adult Sprague‐Dawley rats (6 months old; n = 8) and in aged rats (20 months old; n = 8). Serum levels of ADMA and L‐arginine were measured by high‐performance liquid chromatography and responses of endothelium‐intact aortic rings to acetylcholine (ACh) were tested. Nitric oxide synthase activity in kidney tissue and serum concentrations of nitrite, a stable end‐product of nitric oxide, were assayed and serum contents of malondialdehyde, derived from lipid peroxidation and serum lipid and creatinine level were determined.3. Serum levels of ADMA increased significantly in aged rats compared with adult rats (P < 0.01), whereas serum levels of L‐arginine were similar in both groups (P = NS). Accordingly, the ratio of L‐arginine/ADMA in old rats was lower than that in young rats (P < 0.01). Endothelium‐dependent relaxation responses to ACh in aortic rings from aged rats were impaired and these impaired responses were improved by pre‐incubation of aortic rings with L‐arginine.4. Nitric oxide synthase activity in the kidney, together with serum concentration of nitrite, was significantly decreased and serum contents of malondialdehyde, cholesterol and triglycerides were increased in old compared with young rats. However, the serum creatinine level was not significantly different between adult and aged rats.5. Endogenous ADMA may be a contributor to age‐related endothelial dysfunction and increases in endogenous ADMA may be linked to lipid peroxidation in aged rats.
Prenatal Undernutrition, Glucocorticoids And The Programming Of Adult Hypertension
Authors: Edwards Lisa J , Coulter Catherine L , Symonds Michael E , McMillen I Caroline 
Published: March 2003

SUMMARY1. A range of epidemiological studies has shown that poor intra‐uterine growth is associated with an increased prevalence of cardiovascular disease, non‐insulin‐dependent diabetes mellitus and the Metabolic syndrome in adult life.2. Because these associations are independent of adult lifestyle or current size, it has been postulated that a reduced intra‐ uterine nutrient supply perturbs fetal growth and, concomitantly, alters or programmes the structure and function of developing systems.3. A reduced fetal nutrient supply may be a consequence of poor placental function or inadequate maternal nutrient intake.4. It has been proposed that one outcome of either a suboptimal placental or maternal nutrient supply is exposure of the fetus to excess glucocorticoids, which act to restrict fetal growth and to programme permanent changes in the cardiovascular, endocrine and metabolic systems.5. While a range of studies in the rat has investigated the impact of maternal undernutrition on arterial blood pressure in the offspring, there have been relatively few studies in species, such as the sheep, in which the responses of the cardiovascular and neuroendocrine systems to intra‐uterine undernutrition can be measured before birth.6. The present review summarizes recent evidence that poor placental function or inadequate maternal nutrition each results in an increased exposure of fetal sheep tissues to glucocorticoids and, in specific, changes in the regulation of fetal arterial blood pressure.7. These studies are important in determining how the timing, type and duration of fetal nutrient restriction are each important in determining the nature of the fetal neuroendocrine and cardiovascular adaptive responses and their pathophysiological sequelae in later life.
Does It Make Sense To Develop New Centrally Acting Cardiovascular Drugs?
Authors: Bousquet P , Monassier L , Feldman J 
Published: March 2003

SUMMARY1. The autonomic nervous system plays a pivotal role in modulating all the components of the cardiovascular regulation. Therefore, one can assume that drugs targeting this system may be useful in the management of several cardiovascular diseases.2. Drugs acting on central nervous system centres seem to be modulators rather than blockers; as such, they are expected to preserve the contraregulatory processes and to generate only a few side effects.3. Because the sympathetic nervous system is largely involved in the regulation of vasomotor tone, centrally acting antihypertensive drugs were developed first.4. Recently, new leader compounds selective for non‐ adrenergic imidazoline recepetors have been synthetized. Although such drugs have no capacity to activate α2‐adrenoceptors, they have been proven to be hypotensive. These drugs are expected to be even better tolerated than the currently available centrally active drugs. They may also have additional beneficial effects.5. Here, the experimental evidence suggesting that such drugs may be useful in the management of some cardiac arrhythmias and/or left ventricular dysfunction will be reviewed.
Analysis Of Agonist‐Evoked Nitric Oxide Release From Human Endothelial Cells: Role Of Superoxide Anion
Authors: David‐Dufilho Monique , Brunet Annie , Privat Christelle , Devynck Marie‐Aude 
Published: March 2003

SUMMARY1. Dichlorofluorescein oxidation and electrochemical monitoring of in situ nitric oxide (NO) release from cultured human endothelial cells reveals that agonists such as thrombin and histamine simultaneously stimulate transient superoxide production.2. The duration of ·NO release was increased only in the simultaneous presence of extracellular L‐arginine and exogenous superoxide dismutase. In contrast, the inhibition of membrane reduced nicotinamide adenine dinucleotide (phosphate) oxidases, the major source of ·O2– in endothelial cells, did not prolong ·NO release, although extracellular L‐arginine was also present. Comparison of these two experimental conditions suggested that H2O2 was involved in the extension of the ·NO signal.3. The present study demonstrates that, in the absence of external L‐arginine, ·O2– production does not constitute the major pathway controlling the duration of agonist‐induced ·NO signal. These results suggest that L‐arginine and H2O2 act jointly to maintain nitric oxide synthase in an activated form.