bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXAMINATION OF ADENOSINE RECEPTOR‐MEDIATED RELAXATION OF THE PIG CORONARY ARTERY
Authors: Lew Michael J , Kao Sheau W 
Published: March 2003

1. The adenosine receptors mediating relaxation of porcine isolated left anterior descending coronary arteries (LAD) and the effects of the level and type of preconstriction on the responses to adenosine analogues were examined in the present study.2. Relaxation responses to the non‐selective adenosine receptor agonist N‐ethylcarboxamidoadenosine (NECA) were endothelium independent. N‐Ethylcarboxamidoadenosine, GR 79236 (A1 receptor selective) and 8‐cyclopentyl‐1,3‐dipropylxanthine (CGS 21680) (A2A receptor selective) produced full relaxation in LAD precontracted to 50% of the response to potassium depolarization with the thromboxane receptor agonist U46619. The order of potency was CGS 21680 = NECA > GR 79236, consistent with that defining the A2A receptor subtype.3. 3,7‐Dimethyl‐1‐propargylxanthine (DMPX; A2 receptor selective) competitively antagonized NECA and CGS 21680 with pKB values of 4.95±0.09 and 5.06±0.22, respectively. The A1 receptor selective antagonist 1,3‐[3H]‐dipropyl‐8‐cyclopentylxanthine (DPCPX) had no effect on NECA relaxation, even in the presence of DMPX.4. The sensitivity to relaxation by NECA was dependent on the precontracting agent. Arteries precontracted with endothelin (ET)‐1 were most sensitive to NECA, U46619‐precontracted arteries were intermediate and KCl‐precontracted arteries were least sensitive.5. The potency of NECA was reduced when the preconstriction level was increased from 50 to 90% of maximum in U46619‐precontracted arteries (pEC50 7.94±0.12 and 7.35±0.04, respectively) and, in KCl‐precontracted arteries, both the potency and maximum effect of NECA were reduced when the preconstriction level increased from 50 to 80% of maximum (pEC50 7.52±0.13 and 6.91±0.26, respectively; maximum responses 82.5±10.2 and 23.9±3.6%, respectively, of the preconstricted tone). Relaxation responses to NECA were independent of the level of precontraction in ET‐1‐precontracted arteries.6. In porcine LAD, relaxation responses to adenosine analogues were endothelium independent and were mediated via A2A adenosine receptors. Responses to NECA were dependent on both the level and type of preconstriction.
PHYSIOLOGICAL GENETICS: APPLICATION TO HYPERTENSION RESEARCH
Authors: Jacob Howard J 
Published: March 2003

1. The rapid advancement of the human genome within the next 5–7 years begins a new era for biological research. The structure of all ~100 000 genes will be known, but the function of the majority of these genes will remain unknown. This paper outlines a ‘physiological genetics’ strategy for determining the genetic basis of hypertension by combining a variety of techniques (e.g. genetics, molecular biology, bioinformatics and physiology), to help identify gene function and the pathways involved in the development of hypertension in the rat.2. Using comparative gene mapping, these regions can be used to implicate susceptibility loci for hypertension in humans, resulting in rapid conversion of basic research in animal models to relevant clinical assessment. The present study outlines some new strategies (i.e. whole‐animal physiological genetics) as a means to study disease aetiology in polygenic disorders and to facilitate gene identification in the ascent of functional genomics.
RENAL NERVE AND α2‐ADRENERGIC ACTION DURING ACUTE VOLUME EXPANSION IN THE ANAESTHETIZED RAT
Authors: Young Paul J , Miller John H 
Published: March 2003

1. The effects of renal denervation and α2‐adrenoceptor blockade on diuresis and natriuresis in response to acute volume expansion (VE) were investigated in anaesthetized rats.2. In normal rats, a 30 min intravascular VE of up to 7.5% of bodyweight caused a significant diuresis and natriuresis.3. Denervation enhanced the diuretic effect of VE by 39%, while α2 blockade by 12 μmol/kg per h rauwolscine significantly inhibited the response by 61% in innervated kidneys and 43% in denervated kidneys.4. Similar results were found for natriuresis in both innervated and denervated kidneys.5. The results demonstrate that renal sympathetic nerve activity inhibits part of the increase in sodium and water excretion caused by VE, since denervation increased excretion under these conditions. The contribution of renal nerves to the control of renal function, however, decreases during the response to VE.6. α2‐Adrenoceptor action enhanced the diuretic and natriuretic effects of VE by mechanisms otherwise unrelated to renal nerve activity.
MUSCLE VENOUS PO2 AND V.O2 ARE LINEARLY RELATED IN REPETITIVE TETANIC CONTRACTIONS OF CANINE MUSCLE DURING HYPOXIC HYPOXIA
Authors: Kohzuki H , Misawa H , Kishi T , Ohga Y , Sakata S , Takaki M 
Published: March 2003

1. It has previously been shown that perfusion with high O2‐affinity‐erythrocytes decreases venous PO2 (PVO2) and decreases O2 uptake (V.O2) in contracting muscle at the same O2 delivery (arterial O2 concentration × flow). A linear V.O2–PVO2 relationship has been obtained with a V.O2‐axis intercept, suggesting that, during this type of hypoxia, V.O2 is composed of a PVO2‐dependent and ‐independent V.O2. However, the V.O2– PVO2 relation during hypoxic hypoxia has not been examined.2. To clarify this relation, PVO2 and V.O2 have been measured in contracting gastrocnemius (1 Hz trains of 0.2 s isometric tetani) under both normoxic and hypoxic conditions during 5 min of stimulation.3. Venous O2 changes proportionally with O2 delivery. Each V.O2–PVO2 relation was linear, with the mean described by the equation V.O2 = 5.06 + 0.41 × PVO2 (n = 6, r = 0.81, P < 0.05). The V.O2‐axis intercept was significantly different from zero (P < 0.05).4. These results were similar to those obtained during hypoxia induced by high O2‐affinity‐erythrocytes. We conclude that there is a linear relationship between PVO2 and V.O2 above the V.O2‐axis intercept, regardless of the type of hypoxia.
Molecular Control Of Cell Type Diversity In The Developing Spinal Cord
Authors: Yamada Toshiya , Karunaratne Asanka , Hargrave Murray 
Published: March 2003

SUMMARY1. During embryonic development, a diverse array of neurons and glia are generated at specific positions along the dorso– ventral and rostro–caudal axes of the spinal cord from a common pool of precursor cells.2. This cell type diversity can be distinguished by the spatially and temporally coordinated expression of several transcription factors that are also linked to cell type specification at a very early stage of spinal cord development.3. Recent studies have started to uncover that the generation of cell type diversity in the developing spinal cord. Moreover, distinct cell types in the spinal cord appear to be determined by the spatially and temporally coordinated expression of transcription factors.4. The expression of these factors also appears to be controlled by gradients of factors expressed by ventral and dorsal midline cells, namely Sonic hedgehog and members of the transforming growth factor‐β family.5. Changes in the competence of precursor cells and local cell interactions may also play important roles in cell type specification within the developing spinal cord.
Regulation Of Spinal Motoneuron Differentiation By The Combined Action Of Sonic Hedgehog And Neurotrophin 3
Authors: Dutton Renée , Yamada Toshiya , Turnley Ann , Bartlett Perry F , Murphy Mark 
Published: March 2003

1. The development of ventral cell types in the spinal cord, including motor neurons, requires the growth factor Sonic hedgehog (Shh). However, it is still unknown whether Shh acts directly on precursors to induce these cell types and whether additional factors are required for induction.2. To further investigate the precise role of Shh in spinal motoneuron development, we used low‐density cultures of murine spinal cord precursor cells.3. Although purified Shh stimulated neuronal differentiation, it did not increase the proportion of neurons expressing the motoneuron marker Islet‐1 (Isl‐1). In contrast, purified Shh induced Isl‐1 expression in neural tube explants, suggesting that additional neural tube‐derived factors are required to induce motoneuron differentiation.4. A factor implicated in motoneuron development, neurotrophin 3 (NT3), had no effect on Isl‐1 expression; however, in combination with Shh, it induced Isl‐1 expression in the majority of neurons in the low‐density cultures. Furthermore, in explant cultures, Shh‐induced Isl‐1 expression was blocked by an anti‐NT3 antibody.5. In addition, previous studies have shown expression of NT3 in the region of motoneuron differentiation and the loss of spinal fusimotor neurons in NT3‐knockout animals.6. Taken together, these findings suggest that Shh can act directly on spinal cord precursors to promote neuronal differentiation, but induction of Isl‐1 expression and motor differentiation requires additional factors, including NT3.
Effect Of Glucose Load On The Transport Kinetics Of Palmitic Acid In The Human Placenta: An In Vitro Study
Authors: Nandakumaran M , Al‐Rayyes S , Al‐Yatama M , Sugathan Tn 
Published: March 2003

SUMMARY1. A paucity of data relating to free fatty acid (FFA) transport in the human placenta in non‐steady state conditions prompted us to undertake the present study.2. The transport kinetics of palmitic acid in non‐steady state conditions have been investigated in vitro using human perfused placental lobules. The effects of varying glucose concentrations on maternal–foetal transport of the FFA were also investigated to mimic the hyperglycaemic states of human diabetic pregnancies.3. National Cancer Tissue Culture medium diluted with Earle’s buffered salt solution was used as the perfusate. [14C]‐Palmitic acid, along with tritiated water as a reference, was injected as a bolus into the maternal arterial perfusate and perfusate samples were collected from the venous outflow for a period of 5 min.4. The transport fraction (TF) of palmitic acid, expressed as percentage of the injected bolus, averaged 3.45±0.15% in five perfusions, representing 9.2±1.3% of the corresponding reference marker TF. Kinetic parameters, as well as TF indices of palmitic acid expressed in relation to the reference substance, did not differ significantly between perfusions with a physiological glucose load and those with hyperglycaemic concentrations of glucose of 27.8 and 55.6 mmol/L.5. The present study shows that hyperglycaemia per se does not significantly alter palmitic acid transport kinetics in vitro in the human perfused placental lobule.
EFFECTS OF BILATERAL NEPHRECTOMY AND ANGIOTENSIN II REPLACEMENT ON BODY FLUIDS IN FOETAL SHEEP
Authors: Gibson KAREN J , Lumbers EUGENIE R 
Published: March 2003

1. To determine the importance of the kidneys in maintaining the normal volume and composition of foetal body fluids, measurements were made in 11 chronically catheterized foetuses (123–136 days) that had been bilaterally nephrectomized at least 5 days previously and compared with 10 intact foetuses (121–133 days).2. The nephrectomized foetuses had reduced extracellular (ECV), blood, plasma and interstitial volumes per kg foetal weight (P < 0.005), reduced plasma chloride levels (P < 0.001) and were acidaemic, hypoxaemic and hypercapnaemic (P < 0.05) compared with intact foetuses. They also had reduced lung liquid production (P < 0.05) and reduced lung liquid sodium and osmolality levels (P < 0.05). Their arterial pressure was more variable between foetuses (P < 0.005) and was directly related to ECV/kg (P = 0.013).3. To determine which of these changes were due to absence of the foetal renin–angiotensin system, seven chronically catheterized nephrectomized foetal sheep (124–132 days) were infused with replacement doses of angiotensin (Ang)II (1.5 μg/kg per h) for 3 days. Six nephrectomized foetuses were infused with 0.15 mol/L saline.4. The AngII infusion was non‐pressor. It prevented the fall in ECV that occurred in the control group (P < 0.05) and foetal plasma chloride concentration rose (P < 0.05). Blood gas status and lung liquid production rate did not change, but lung liquid sodium concentration fell (P < 0.05) and potassium concentration rose (P < 0.05).5. Bolus injections of AngII (0.3–5 μg) were given to assess vascular sensitivity to AngII. This was not altered by either nephrectomy or AngII replacement.6. It is concluded that the foetal kidneys are important for the maintenance of the normal volume and composition of foetal body fluids. Angiotensin II, perhaps because it promotes fluid transfer across the placenta, helps maintain foetal ECV and plasma chloride levels.
ENDOTHELIN IN THE CENTRAL CONTROL OF CARDIOVASCULAR AND RESPIRATORY FUNCTIONS
Authors: Kuwaki T , Ling Gy , Onodera M , Ishii T , Nakamura A , Ju Kh , Cao Wh , Kumada M , Kurihara H , Kurihara Y , Yazaki Y , Ohuchi T , Yanagisawa M , Fukuda Y 
Published: March 2003

SUMMARY1. Exogenously administered endothelin (ET) modulates the activity of cardiovascular and respiratory neurons in the central nervous system (CNS) and, thus, affects arterial blood pressure (ABP) and ventilation. However, a physiological role(s) for endogenous ET in the CNS has not been elucidated. To address this question, we examined ABP and ventilation in mutant mice deficient in ET‐1, ETAand ETBreceptors and endothelin‐ converting enzyme‐1, which were made by gene targeting.2. Respiratory frequency and volume was measured in mice by whole body plethysmography when animals breathed normal room air and hypoxic and hypercapnic gas mixtures. A few days after respiratory measurements, a catheter was implanted into the femoral artery under halothane anaesthesia. On the following day, the ABP of awake mice was measured through the indwelling catheter and heart rate was calculated from the ABP signal. After 2 h ABP measurement, arterial blood was collected through the catheter and pH and the partial pressures of O2and CO2were measured by a blood gas analyser.3. Compared with corresponding controls, the mean (±SEM) ABP in ET‐1+/–and ETB‐deficient mice was significantly higher (118±2vs106±3 mmHg for ET‐1+/–(n= 22) and ET‐1+/+(n= 17) mice, respectively; 127±3vs109±4 mmHg for ETB–/s(n= 9) and ETB+/s(n= 9) mice, respectively;P<0.05 for both). In ET‐1+/–mice,PCO2tended to be higher andPO2was significantly lower than corresponding values in ET‐1+/+mice. Under resting conditions, there was no significant difference in respiratory parameters between mutants and their corresponding controls. However, reflex increases of ventilation to hypoxia and hypercapnia were significantly attenuated in ET‐1+/–, ET‐1–/–and ETA–/–mice.4. In another series of experiments in ET‐1+/–mice, we found that sympathetic nerve activity (SNA) was augmented and reflex excitation of phrenic nerve activity (PNA) in response to hypoxia and hypercapnia was blunted. Attenuation of the reflex PNA response to hypercapnia was also observed in the medulla–spinal cord preparation from ET‐1–/–mice.5. Elevation of ABP in ETB‐deficient mice was most likely due to a peripheral mechanism, because SNA and respiratory reflexes were not different from those in control animals.6. We conclude that endogenous ET‐1 plays an important role in the central neural control of circulation and respiration and that ETAreceptors mediate this mechanism.
ENDOTHELIN AND POST‐GANGLIONIC SYMPATHETIC NEURONS
Authors: Damon Deborah H 
Published: March 2003

SUMMARY1. The present report documents evidence suggesting that endothelin (ET) is a mediator and modulator of post‐ganglionic sympathetic neuronal development.2. Endothelin is produced by post‐ganglionic neurons and by cells adjacent to these neurons.3. Post‐ganglionic sympathetic neurons express functional receptors for ET.4. Endothelin promotes the survival of cultured post‐ ganglionic sympathetic neurons and modulates the morphological and biochemical differentiation of these neurons.5. Endothelin enhances the activity of nerve growth factor and modulates the release of neurotransmitter from post‐ ganglionic sympathetic nerve terminals.
Long‐Term Oestrogen Therapy Is Associated With Improved Endothelium‐Dependent Vasodilation In The Forearm Resistance Circulation Of Biological Males*
Authors: New Gishel , Duffy Stephen J , Harper Richard W , Meredith Ian T 
Published: March 2003

SUMMARY1. The aim of the present study was to determine the effects of long‐term oestrogen on resistance vessel reactivity in biological males.2. Recent studies have demonstrated that long‐term oestrogen therapy favourably alters the lipid profile and improves vasodilator function in the conduit arteries of biological males. Whether a similar benefit is exerted on the resistance circulation is not known. Therefore, we examined the effects of long‐term oestrogen therapy on skeletal muscle resistance vessel function in biological males and the potential mechanisms by which it may exert its effects.3. Forearm blood flow (FBF) and resistance were compared in 15 male‐to‐female transsexuals being prescribed oestrogen, with 14 age‐matched healthy males, at rest and in response to the endothelium‐dependent nitric oxide (NO) vasodilator acetylcholine (ACh), the endothelium‐independent but NO‐mediated vasodilator sodium nitroprusside (SNP), the endothelium‐ independent and non‐NO‐mediated vasodilator verapamil (VER) and the endothelium‐independent vasoconstrictor phenylephrine (PE).4. Basal blood flows were similar in the two groups. However, the male‐to‐female transsexuals had a significant upward and leftward shift in FBF responses to ACh compared with males, with a 52% increase in FBF responses at the highest dose of ACh used. Forearm blood flow in transsexuals rose from a mean (±SEM) baseline level of 3.02±0.25 to a maximum of 19.5± 2.59 mL/min per 100 mL forearm tissue (compared with 3.24±0.41 and 9.43±1.97 mL/min per 100 mL forearm tissue, respectively, in males) with the highest dose of ACh (+2.73 μg/min per 100 mL; P < 0.0005). Forearm vascular resistance was also significantly reduced in transsexuals compared with males (P < 0.05). Vasodilator responses to SNP, VER and PE were similar in both groups.5. There were no differences observed in total cholesterol and low‐density lipoprotein–cholesterol levels. However, male‐ to‐female transsexuals had 20% higher high‐density lipo‐protein–cholesterol levels compared with males (1.57±0.11 vs 1.26±0.08 mmol/L, respectively; P < 0.05) and 47% higher triglyceride levels (P < 0.005). Serum testosterone levels (an index of oestrogen therapy) was a predictor of responses to endothelium‐dependent vasodilation (rs = –0.50; P < 0.01).6. Long‐term oestrogen therapy enhances endothelium‐dependent vasodilation in the skeletal muscle microcirculation of biological males. The effects appear to be selective because endothelium‐independent vasodilation and vasoconstriction are not altered.
Effect Of Chronic Lithium Administration On Endothelium‐Dependent Relaxation In Rat Aorta
Authors: Dehpour Ahmad Reza , Aghadadashi Hamid , Ghafourifar Pedram , Roushanzamir Farshad , Ghahremani Mohammad Hossein , Meysamee Farnoush , Rassaee Nastaran , Koucharian Armen 
Published: March 2003

SUMMARY1. The effects of chronic lithium administration on the relaxant responses of rat thoracic aortic rings in the presence of indomethacin (a cyclo‐oxygenase inhibitor) and/or NG‐nitro‐L‐arginine (L‐NOARG; a nitric oxide synthase inhibitor) to acetylcholine (ACh) or sodium nitroprusside were investigated in the present study.2. Acetylcholine produced a concentration‐dependent relaxation in vessels precontracted by phenylephrine (PE), while in lithium‐treated rats the maximal relaxation was significantly increased.3. Indomethacin (20 μmol/L) significantly potentiated the ACh‐induced relaxation in lithium‐treated and control rats.4. NG‐Nitro‐L‐arginine (1 μmol/L) decreased the ACh‐induced relaxation in both control and lithium‐treated rats. In contrast, indomethacin (20 μmol/L) reversed the inhibitory effect of L‐NOARG.5. Sodium nitroprusside produced similar concentration‐dependent relaxations of vessels from both control and lithium‐treated rats, which was not affected by indomethacin. In endothelium‐denuded rings, indomethacin (20 μmol/L) caused a rightward shift in the concentration–contraction curve to PE.6. These data support evidence for a possible increase in endothelium‐dependent relaxation induced by ACh during long‐term administration of lithium in rat aortic rings.
Oxidative Status And Anti‐Oxidant Enzyme Activity During Calcium Paradox In The Rat Isolated Heart
Authors: Lazou Antigone , Seraskeris Stelios , Tsiona Vasiliki , Drossos George 
Published: March 2003

SUMMARY1. The effect of calcium paradox on oxidative status and the activity of anti‐oxidant enzymes were studied in the rat isolated heart. Glutathione status, sulphydryl group contents and lipid peroxidation in the myocardium, as well as the release of oxidized and reduced glutathione from the heart, were taken as indices of oxidative events.2. Reperfusion with calcium after calcium‐free perfusion induced a significant decrease in the myocardial content of reduced and oxidized glutathione and non‐protein sulphydryl groups. At the same time, a significant release of both forms of glutathione from the heart was observed. However, the ratio of oxidized to reduced glutathione remained unchanged and was not different from control. Increased lipid peroxidation was observed only after 30 min of reperfusion with calcium.3. Increased anti‐oxidant activity during the reperfusion period was observed. Mitochondrial Mn‐superoxide dismutase (SOD) activity was increased throughout the reperfusion period, while cytoplasmic Cu,Zn‐SOD and glutathione peroxidase activity showed a transient increase at 5 min reperfusion.4. The results do not support an important role of oxygen free radicals in cell damage observed during calcium paradox in the rat isolated heart. Production of oxygen free radicals may occur during the reperfusion period, but the quantity produced is insufficient to exceed the anti‐oxidant capacity of the heart.
Krn2391: Dual Action On Rat Pulmonary Artery And No Loss Of Potency In Pulmonary Hypertension
Authors: Wanstall Janet C , Gambino Agatha , Thomas Bronwyn J 
Published: March 2003

SUMMARY1. The pulmonary vasorelaxant properties of KRN2391 (N‐cyano‐N′‐(2‐nitroxyethyl)‐3‐pyridinecarboximidamide) were examined in isolated ring preparations of main (MPA) and intralobar (IPA) pulmonary artery from control and pulmonary hypertensive rats (exposure to hypoxia, 10% oxygen, for 1 week).2. On both MPA and IPA, pulmonary vasorelaxant responses were inhibited by methylene blue (10 μmol/L) or glibenclamide (1 or 10 μmol/L). Thus, KRN2391 has the properties of both a nitric oxide (NO) donor and a KATP channel opener on rat pulmonary arteries.3. KRN2391 was more potent and gave a greater maximum relaxation on MPA (–log EC50 6.47; maximum 92% reversal of induced contraction) than on IPA (–log EC50 6.09; maximum 58% reversal of induced contraction). Comparable differences between MPA and IPA were seen for SIN‐1 (NO donor) and levcromakalim (KATP channel opener).4. KRN2391 was equipotent in MPA from control and pulmonary hypertensive rats but, when glibenclamide (10 μmol/L) was present, KRN2391 was six‐fold less potent in preparations from pulmonary hypertensive than control rats. An eight‐fold reduction in potency was seen for SIN‐1 (no glibenclamide) in arteries from pulmonary hypertensive rats, confirming previous findings with other NO donors.5. It is concluded that the dual mechanism of action of KRN2391 accounts for the finding that this drug is equally potent in pulmonary arteries from pulmonary hypertensive and control rats. In the context of pulmonary hypertension, this property of the drug could give it an advantage over drugs that act solely as NO donors because these decline in potency, at least in animal models of this disease.