bluuebunny/crossref_metadata_2025_split huggingface dataset:
Purinoceptor‐mediated contractility of the perfused uterine vasculature of the guinea‐pig: influence of oestradiol and pregnancy
Authors: Haynes John M , Pennefather Jocelyn N , Sikorski Bogdan 
Published: July 2003

Summary1. The effects of ATP, the stable ATP analogues α,β‐methylene ATP (α,β‐mATP), 2‐methylthioATP (2meSATP) and adenosine tetraphosphate (ATP4), the pyrimidine nucleotide uridine 5′‐triphosphate (UTP) and the α1‐adrenoceptor agonist phenylephrine were examined on the isolated perfused uterine vasculature of dioestrous, oestradiol‐treated, dexamethasone‐treated and late‐pregnant guinea‐pigs.2. The α1‐adrenoceptor agonist phenylephrine elicited concentration‐dependent vasoconstriction from preparations of perfused uterine vasculature from dioestrous, estradiol‐treated and late‐pregnant guinea‐pigs. The mean maximal response to phenylephrine was unaffected by treatment of dioestrus guinea‐pigs with oestradiol or dexamethasone, but was reduced in preparations from late‐pregnant animals.3. In perfused uterine arteries from dioestrous animals, the pyrimidine UTP, but not ATP4 and ATP, elicited vasoconstrictor responses. In preparations from oestradiol‐treated animals, all three agonists elicited vasoconstriction, with a rank order of potency of ATP4 = UTP ≫ ATP, whereas in preparations from late‐pregnant animals this order of potency was ATP4 ≫ UTP = ATP. In preparations from dexamethasone‐treated animals, the vasoconstriction was similar to that seen in dioestrous animals. Vasoconstrictor responses to ATP4 were significantly greater in preparations of uterine vasculature from oestradiol‐treated and pregnant animals than in preparations from dioestrous animals or dexamethasone‐treated animals.4. In preparations from dioestrous, oestradiol‐treated, pregnant and dexamethasone‐treated animals, α,β‐mATP was approximately two to three orders of magnitude more potent than 2meSATP. Compared with preparations from dioestrous animals, the maximal responses to α,β‐mATP were significantly greater in tissues from oestradiol‐treated and pregnant animals. In preparations from dioestrous animals, the P2 purinoceptor antagonist suramin (100 µmol/L) inhibited the responses to α,β‐mATP, but not those to ATP4.5. The present study has demonstrated that pregnancy, but not the steroid treatment of dioestrous guinea‐pigs with oestradiol or dexamethasone, reduces the sensitivity of the guinea‐pig isolated perfused uterine vasculature to phenylephrine. In contrast, preparations from pregnant or oestradiol‐treated guinea‐pigs respond to ATP4 and to α,β‐mATP with significantly greater constrictions than those of dioestrous or dexamethasone‐treated animals. These data indicate that the sensitivity of the uterine vasculature to adrenoceptor and purinoceptor agonists is differentially regulated by oestradiol and pregnancy, but not by the synthetic glucocorticoid dexamethasone.
Apoptosis is involved in the cardiac damage induced by sinoaortic denervation in rats
Authors: Tao Xia , Zhang Shu‐Hui , Chu Zheng‐Xu , Su Ding‐Feng 
Published: July 2003

Summary1. The arterial baroreflex plays an important role in the maintenance of the stability of blood pressure. Sinoaortic denervation (SAD) produces severe organ damage in rats. The present study was designed to investigate whether apoptosis, which is a ubiquitous physiological mode of cell death distinct from cell mortality induced by injury and necrosis, is involved in SAD‐induced cardiac damage.2. Male Sprague‐Dawley rats (10 weeks old) were used. Rats underwent SAD (n = 9) or sham operation (n = 10). Sixteen weeks after operation, the heart tissues were taken for investigations including electron microscopy, immunohistochemistry, terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick‐end labelling (TUNEL) and reverse transcription–polymerase chain reaction (RT‐PCR).3. Cardiac hypertrophy and fibrosis was found in SAD rats. The number apoptotic cardiomyocytes was increased in SAD rats compared with sham‐operated rats.4. The expression of Bcl‐2mRNA and protein (an inhibitory factor of apoptosis) in cardiomyocytes was decreased in SAD rats. In contrast, the expression of Bax, Fas and Fas ligand mRNA and proteins (promoters of apoptosis) in cardiomyocytes was significantly increased in SAD rats.5. In conclusion, the present study reveals a high level of apoptosis in cardiomyocytes in SAD rats. It is proposed that apoptosis is involved in SAD‐induced cardiac damage.
Haemodynamic action of B‐type natriuretic peptide substantially outlasts its plasma half‐life in conscious dogs
Authors: Thomas Colleen J , Woods Robyn L 
Published: July 2003

Summary1. The objective of the present study was to determine the plasma half‐life of B‐type natriuretic peptide (BNP) in conscious dogs after intravenous administration and to compare this with its haemodynamic effects. In six chronically instrumented dogs, plasma BNP concentrations were measured under basal conditions, during a constant infusion of canine BNP‐32 (10 pmol/kg per min; 25 min) to steady state and at nominated time points up to 75 min after stopping the infusion. Concomitant, continuous measurements of mean arterial blood pressure (MAP), heart rate (HR), central venous pressure (CVP) and mesenteric blood flow (MBF) were obtained.2. Baseline plasma BNP levels were 15.0 ± 2.3 fmol/mL and rose approximately 10‐fold to 159 ± 23 fmol/mL after 20–25 min BNP infusion. When the infusion was turned off, plasma BNP levels declined in a biphasic manner, with an initial half‐life of 1.57 ± 0.14 min and a terminal half‐life of 301 ± 85 min. The metabolic clearance rate of BNP was 2.29 ± 0.34 L/min.3. The infusion of BNP reduced MAP (approximately 10%), CVP (approximately 65%) and MBF (approximately 25%), whereas haematocrit (approximately 4%) and mesenteric vascular resistance (MVR) increased (approximately 40%; all P < 0.05). Plasma BNP levels returned to baseline by 20 min after BNP infusion had been stopped, whereas none of the haemodynamic variables returned to normal by this time. Mean arterial pressure returned to resting levels within 10–15 min after plasma BNP returned to normal. However, CVP, haematocrit and MBF remained substantially below baseline values for more than 20 min after circulating BNP levels had returned to pre‐infusion levels. Of these, only mesenteric vascular changes were returned to baseline within 60 min of plasma BNP levels normalizing.4. These results demonstrate that the removal of BNP from the canine circulation is rapid, similar to observations made regarding the metabolism of circulating atrial natriuretic peptide in dogs. The half‐life of BNP in dogs was shorter than that in rats, sheep or humans. However, the haemodynamic actions of BNP substantially outlasted its plasma half‐life. Whether this disparity in plasma level and haemodynamic activity of BNP reflects long‐lasting activation of second messenger systems or slow recovery from the hydraulic changes at the capillary level, reflected in the haematocrit and CVP, remains to be answered.
Effect of Centella asiatica on cognition and oxidative stress in an intracerebroventricular streptozotocin model of Alzheimer's disease in rats
Authors: Veerendra Kumar MH , Gupta YK 
Published: July 2003

Summary1. Centella asiatica, an Indian medicinal plant, has been described as possessing central nervous system activity, such as improving intelligence. In addition, we have demonstrated that C. asiatica has cognitive‐enhancing and anti‐oxidant properties in normal rats. Oxidative stress or an impaired endogenous anti‐oxidant mechanism is an important factor that has been implicated in Alzheimer's disease (AD) and cognitive deficits seen in the elderly.2. Intracerebroventricular (i.c.v.) streptozotocin (STZ) in rats has been likened to sporadic AD in humans and the cognitive impairment is associated with free radical generation in this model. Therefore, in the present study, the effect of an aqueous extract of C. asiatica (100, 200 and 300 mg/kg for 21 days) was evaluated in i.c.v. STZ‐induced cognitive impairment and oxidative stress in rats.3. Male Wistar rats were injected with STZ (3 mg/kg, i.c.v.) bilaterally on the days 1 and 3. Cognitive behaviour was assessed using passive avoidance and elevated plus‐maze paradigms on the days 13, 14 and 21. Rats were killed on the day 21 for estimation of oxidative stress parameters (malondialdehyde (MDA), glutathione, superoxide dismutase and catalase) in the whole brain upon completion of the behavioural task.4. Rats treated with C. asiatica showed a dose‐dependent increase in cognitive behaviour in both paradigms. A significant decrease in MDA and an increase in glutathione and catalase levels were observed only in rats treated with 200 and 300 mg/kg C. asiatica.5. The present findings indicate that an aqueous extract of C. asiatica is effective in preventing the cognitive deficits, as well as the oxidative stress, caused by i.c.v. STZ in rats.
Myocardial adenosine does not correlate with the protection mediated by ischaemic or pharmacological preconditioning in rat heart
Authors: Vasara Eleni , Katharou Ioanna , Lazou Antigone 
Published: July 2003

Summary1. We tested the hypothesis that ischaemic preconditioning of the rat heart activates cardiovascular adenosine formation to provide enhanced cardioprotection.2. Rat isolated perfused hearts were either non‐preconditioned, preconditioned with 5 min ischaemia or treated for 5 min with the α1‐adrenoceptor agonist phenylephrine (50 µmol/L) before being subjected to 30 min sustained ischaemia followed by 30 min reperfusion. Isolated cardiomyocytes were either non‐preconditioned, subjected to 10 min simulated ischaemia or treated for 10 min with phenylephrine (50 µmol/L) before being subjected to 30 min simulated ischaemia. Functional recovery of hearts and cell viability were used as indices of the effects of ischaemia.3. Myocardial adenosine, as well as intracellular pH, was determined at the end of the preconditioning period and at 10, 20 and 30 min of sustained ischaemia. Intracellular pH was also determined during the reperfusion.4. Ischaemic or pharmacological preconditioning with phenylephrine correlated with an improved functional recovery of perfused hearts during reperfusion and increased cell viability during ischaemia.5. In perfused hearts, ischaemic preconditioning resulted in increased adenosine production in the myocardium during the following sustained ischaemia. However, in isolated cardiomyocytes, adenosine levels during sustained ischaemia were lower in ischaemically preconditioned cells compared with the respective non‐preconditioned cardiomyocytes.6. The increase in adenosine production was not observed in hearts preconditioned with phenylephrine instead of transient ischaemia. Similarly, pharmacological preconditioning resulted in decreased adenosine levels during sustained ischaemia in isolated cardiomyocytes.7. Intracellular pH was preserved during ischaemia to the same extent in both ischaemically or pharmacologically preconditioned hearts and cardiomyocytes, indicating that less acidosis during ischaemia is related to protection.8. Taken together, the results suggest that cardioprotection does not necessarily correlate with increased adenosine production. Thus, adenosine concentration is not crucial to the beneficial effects of preconditioning in rat heart.
Placental endothelial nitric oxide synthase localization and expression in normal human pregnancy and pre‐eclampsia
Authors: Orange SJ , Painter D , Horvath J , Yu B , Trent R , Hennessy A 
Published: July 2003

Summary1. The aim of the present study was to investigate whether pre‐eclampisa, a state of placental hypoxia, is associated with placental abnormalities in the amount, distribution and expression of enothelial nitric oxide synthase (eNOS).2. Localization and intensity of eNOS was determined by immunohistochemistry using an antibody specific for eNOS. The amount of eNOS mRNA expression was determined by reverse transcription–polymerase chain reaction (RT‐PCR) and the densitometry of gel bands was expressed as a ratio of the band density of the housekeeping gene β2‐microglobulin.3. Endothelial NOS staining was localized to syncytiotrophoblast cells within the villi and decidual trophoblast cells. It was not present in the endothelium of terminal villous vessels. There was no significant difference in eNOS villous or decidual staining intensity between normal pregnancy (NP; n = 12), pre‐eclampsia (n = 14), or gestational hypertension (GH; n = 4). Staining for eNOS was not significantly different in the decidua compared with the villi in NP, GH or pre‐eclampsia. Within the decidua, the depth of eNOS staining was similar in NP, pre‐eclampisa and GH.4. There was no significant difference in eNOS mRNA expression between NP (0.70 ± 0.11), pre‐eclampsia (0.5 ± 0.07) or GH (0.69 ± 0.26).5. These findings suggest that the amount of eNOS in the placenta is not deficient in pre‐eclampsia, excluding a possible pathogenic role for eNOS in this disease. Furthermore, placental hypoxia, which is associated with pre‐eclampsia, did not induce an upregulation of eNOS
Role of copper in the relaxant action of S‐nitrosothiols in the rat anococcygeus muscle
Authors: Ng Chi Wai , Najbar‐Kaszkiel Alicja T , Li Chun Guang 
Published: July 2003

Summary1. The effects of copper chelators were investigated on the relaxant actions of the S‐nitrosothiols S‐nitrosoglutathione (GSNO) and S‐nitroso‐N‐acetyl‐d,l‐penicillamine (SNAP), the non‐S‐nitrosothiol nitric oxide (NO) donor sodium nitroprusside (SNP), free radical NO (NO·) and the nitrergic neurotransmitter in rat isolated anococcygeus muscle.2. Cumulative additions of GSNO (0.01–100 µmol/L), SNAP (0.001–10 µmol/L), SNP (0.001–1 µmol/L) and NO· (0.5–5 µmol/L) and electrical field stimulation (EFS; 1–5 Hz, 10 s) of nitrergic nerves in preparations precontracted with guanethidine (10–30 µmol/L) and clonidine (0.01–0.3 µmol/L) produced concentration‐dependent relaxations.3. The Cu[I] chelator neocuproine (10–30 µmol/L) produced concentration‐dependent inhibitions of the relaxations to GSNO and SNAP. At 30 µmol/L, neocuprinone had no effect on relaxations to SNP (0.001–1 µmol/L), NO· (0.5–5 µmol/L) or EFS (1–5 Hz, 10 s).4. The Cu[II] chelator cuprizone (30 µmol/L) slightly and significantly enhanced relaxations to GSNO and NO·, but had no effect on relaxations to SNAP, SNP or EFS.5. In conclusion, the results indicate that Cu[I], but not Cu[II], may be involved in the relaxant actions of GSNO and SNAP in the rat anococcygeus muscle.
Effects of mild aerobic physical exercise on membrane fluidity of erythrocytes in essential hypertension
Authors: Tsuda Kazushi , Yoshikawa Akiyoshi , Kimura Keizo , Nishio Ichiro 
Published: July 2003

Summary1. The present study was undertaken to investigate the effects of aerobic physical exercise on membrane function in mild essential hypertension.2. Hypertensive patients were divided into an exercise group (n = 8) and a non‐exercise (control) group (n = 8). Physical exercise within the intensity of the anaerobic threshold level was performed twice a week for 6 months. Membrane fluidity of erythrocytes was examined by means of electron paramagnetic resonance (EPR) and spin‐labelling methods before and after the trial period in both groups.3. After physical exercise, blood pressure decreased significantly.4. Compared with the non‐exercise group, in the exercise group both the order parameter (S) and the peak height ratio (ho/h‐1) in the EPR spectra of erythrocytes were significantly reduced (S, 0.717 ± 0.004 vs 0.691 ± 0.008, respectively (n = 8), P < 0.05; ho/h‐1, 5.38 ± 0.06 vs 4.89 ± 0.06, respectively (n = 8), P < 0.05). These findings indicated that exercise increased membrane fluidity and improved the membrane microviscosity of erythrocytes.5. There was no direct correlation between blood pressure reduction and the exercise‐induced increase in membrane fluidity of erythrocytes.6. In the non‐exercise (control) group, blood pressure and membrane fluidity were not changed after a 6 month follow‐up period.7.  The results show that aerobic physical exercise increased erythrocyte membrane fluidity and improved the rigidity of cell membranes in hypertensive patients. The improvement of rheological properties of erythrocytes may explain, in part, the cellular mechanisms for the beneficial effects of physical exercise in hypertension.
Magnolol protects against cerebral ischaemic injury of rat heatstroke
Authors: Chang CP , Hsu YC , Lin MT 
Published: July 2003

Summary1. Free radicals mediate cerebral ischaemic injury associated with heatstroke. Magnolol, an active component of Magnolia officinalis, is 1000‐fold more potent than α‐tocopherol in inhibiting lipid peroxidation in rat mitochondria. The aim of the present study was to ascertain whether magnolol attenuated cerebral ischaemic injury and free radical formation associated with heatstroke.2. Urethane‐anaesthetized rats were exposed to heat stress (ambient temperature 42°C) to induce heatstroke. Controlled rats were exposed to 24°C. Mean arterial pressure, cerebral perfusion pressure and cerebral blood flow after the onset of heatstroke were all significantly lower than in control rats. However, colonic temperature, intracranial pressure, heart rate, cerebral free radicals, lipid peroxidation and the neuronal damage score were greater after the onset of heatstroke.3. Magnolol (20 or 40 mg/kg, i.v.) significantly attenuated the heatstroke‐induced hyperthermia, arterial hypotension, intracranial hypertension, cerebral ischaemia and neuronal damage and increased free radical formation and lipid peroxidation in the brain. The extracellular concentrations of ischaemic (e.g. glutamate and lactate/pyruvate ratio) and damage (e.g. glycerol) markers in the corpus striatum were increased after the onset of heatstroke. Magnolol significantly attenuated the increase in striatal ischaemia and damage markers associated with heatstroke.4. Thus, it appears that magnolol has impressive effects against heatstroke reactions.
Effects of an endogenous nitric oxide synthase inhibitor on phorbol myristate acetate‐induced acute lung injury in rats
Authors: Lin Hen I , Chu Shi Jye , Wang David , Chen Hsing I , Hsu Kang 
Published: July 2003

Summary1. In the present study, we determined whether the endogenous nitric oxide (NO) synthase (NOS) inhibitor Nω‐nitro‐l‐arginine methyl ester (l‐NAME) could ameliorate the acute lung injury (ALI) induced by phorbol myristate acetate (PMA) in rat isolated lung.2. Typical ALI was induced successfully by PMA during 60 min of observation. At 2 µg/kg, PMA elicited a significant increase in microvascular permeability (measured using the capillary filtration coefficient Kfc), lung weight gain, lung weight/bodyweight ratio, pulmonary arterial pressure (PAP) and protein concentration of bronchoalveolar lavage fluid.3. Pretreatment with the NOS inhibitor l‐NAME (5 mmol/L) significantly attenuated ALI. None of the parameters reflective of lung injury showed significant increase, except for PAP (P < 0.001). The addition of l‐arginine (4 mmol/L) blocked the protective effective of l‐NAME. Pretreatment with l‐arginine exacerbated PMA‐induced lung injury.4. These data suggest that l‐NAME significantly ameliorates ALI induced by PMA in rats, indicating that endogenous NO plays a key role in the development of lung oedema in PMA‐induced lung injury.
Evaluation of Withania somnifera in a middle cerebral artery occlusion model of stroke in rats
Authors: Chaudhary Geeta , Sharma Uma , Jagannathan Naranamangalam R , Gupta Yogendra K 
Published: July 2003

Summary1. Stroke causes brain injury in millions of people worldwide each year. Despite the enormity of the problem, there is currently no approved therapy that can reduce infarct size or neurological disability. One of the approaches that can be used in limiting the neurological damage after stroke is the use of prophylactic treatment in patients with a high‐risk of stroke. The present study was undertaken to investigate the effect of the Indian herbal plant Withania somnifera as a prophylactic treatment in the middle cerebral artery (MCA) occlusion model of stroke in rats.2. Two groups of male Wistar rats were pretreated with a hydroalcoholic extract of W. somnifera (1 g/kg, p.o.) for 15 and 30 days. Thereafter, rats were subjected to focal ischaemia by occlusion of the MCA using an intraluminal thread. After 2 h MCA occlusion, reperfusion was allowed by retracting the thread. Animals were assessed for ischaemic changes using diffusion‐weighted imaging 30 min after reperfusion. Twenty‐four hours later, rats were subjected to motor performance tests and were subsequently killed for the estimation of the marker of oxidative stress malondialdehyde (MDA). The control group received vehicle and a similar protocol was followed.3. Significant motor impairment, with elevated levels of MDA, was observed in vehicle‐treated MCA‐occluded rats. In addition, diffusion‐weighted imaging showed increased signal intensity in the right hemisphere compared with the contralateral hemisphere. Treatment with W. somnifera for 15 days did not improve motor performance or decrease the elevated levels of MDA. However, when the pretreatment time of W. somnifera was increased to 30 days, it prevented motor impairment and significantly decreased the raised levels of MDA compared with vehicle‐treated rats. In the W. somnifera (30 days)‐pretreated group, the percentage hemispheric lesion area in diffusion‐weighted imaging was significantly attenuated (17 ± 2%) compared with the vehicle‐treated MCA‐occluded group (30 ± 4%).4. Because W. somnifera has been documented to have anti‐oxidant properties, the protection afforded by W. somnifera could be due to its anti‐oxidant effect. The present study provides first evidence of the effectiveness of an Indian herb in focal ischaemia.