bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHYSICAL AND BIOCHEMICAL PREDICTORS OF DEATH IN AN AUSTRALIAN ABORIGINAL COHORT
Authors: McDonald Stephen P , Wang Zhiqiang , Hoy Wendy E 
Published: March 2003

1. Predictors of natural and cardiovascular death were examined in a cohort from a remote Australian Aboriginal community with high mortality rates. The cohort was marked by high prevalences of diabetes (17%), hypertension (19% diastolic blood pressure (BP) > 90 mmHg), obesity (16% body mass index (BMI) > 30), albuminuria (26% albumin/creatinine ratio (ACR) ≥ 34 g/mol) and renal failure (26% calculated glomerular filtration rate < 80 mL/min).2. Relationships between baseline characteristics and subsequent mortality were examined using multivariate techniques.3. Albuminuria, diabetes and hypertension (but not smoking dyslipidaemia or obesity) were all markers for increased risk of natural and especially of cardiovascular death. Age‐ and sex‐adjusted relative risk [95% CI] of natural deaths were 4.3 [1.9–9.5] for overt albuminuria (ACR ≥ 34, 3.2 (range 1.6–6.5) for diastolic BP ≥ 100 and 3.7 (range 1.5–8.9) for diabetes.4. The relative risk associated with albuminuria was independent of diabetes and hypertension. Albuminuria was more common than either diabetes or hypertension and represents a target for intervention to reduce not only progression to renal disease, but also overall mortality.
Gender‐Specific Inhibition of Ca2+ Entry Mechanisms of Arterial Vasoconstriction by Sex Hormones
Authors: Crews Janice K , Khalil Raouf A 
Published: March 2003

SUMMARY1. The clinical observation that hypertension is more common in males and postmenopausal women than in premenopausal women suggests vascular protective effects of female sex hormones, including hormone‐mediated inhibition of vascular tone. The purpose of the present study was to investigate whether the Ca2+ mobilization mechanisms of vascular smooth muscle contraction are modified by gender and sex hormones.2. Active stress and [45Ca2+] influx were measured in de‐endothelialized aortic strips isolated from intact and gonadectomized male and female Sprague‐Dawley rats. In normal Krebs’ (2.5 mmol/L Ca2+), both phenylephrine (Phe; 10–5 mol/L) and membrane depolarization by 96 mmol/L KCl increased active stress to 15.5±1.3 × 10
3 and 14.8±1.2 × 10
3 N/m
2, respectively, and Ca2+ influx to 28.4±1.4 and 32.3±1.5 μmol/kg per min, respectively, in intact males. The Phe‐ and KCl‐induced stress and Ca2+ influx were significantly reduced in intact females. Gonadectomy was associated with no significant changes in the Phe‐ and KCl‐induced stress and Ca2+ influx in males, but was associated with significant enhancement in females. In Ca2+‐free (2 mmol/L EGTA) Krebs’, stimulation of intracellular Ca2+ release by Phe or caffeine (25 mmol/L) caused a transient contraction that was not significantly different in all groups of rats.3. Exogenous application of 17β‐oestradiol, progesterone or testosterone to aortic strips caused concentration‐dependent inhibition of Phe‐ and KCl‐stimulated contractions and Ca2+ influx. 17β‐Oestradiol was the most effective hormone and its relative potency was intact males, castrated males and ovariectomized females > intact females.4. Thus, vascular reactivity and Ca2+ entry in aortic smooth muscle are reduced in the presence and enhanced in the absence of female gonads. Both male and female sex hormones cause vascular relaxation, mainly by inhibiting Ca2+ entry, with oestrogen being the most effective, particularly in the absence of female gonads. The results suggest that a cellular mech‐ anism of oestrogen‐induced vascular relaxation involving inhibition of Ca2+ entry into vascular smooth muscle is gender dependent.
Changes In Cell Volume Induced By Ion Channel Flux In Guinea‐Pig Cardiac Myocytes
Authors: Sasaki N , Takano M , Mitsuiye T , Noma A 
Published: March 2003

SUMMARY1. The cell width of guinea‐pig ventricular myocytes was measured using an optic device during patch‐clamp experiments and the relationship between the ion channel flux and changes in cell volume was examined.2. On superfusing myocytes with 50, 70, 150 and 200% osmotic solutions, the relative cell width changed to 121.1 (n = 4), 110.8 (n = 27), 87.1 (n = 6) and 82.6% (n = 6) of control, respectively. Changes in cell length were less than 2% in these test solutions.3. The application of 300 nmol/L isoprenaline to myocytes swollen in the 70% hypotonic solution induced a decrease in cell width from 111.2 to 106.2% (n = 13). The application of isoprenaline in the isotonic solution also induced a decrease in cell width to 96.5% in eight of 13 cells. A membrane depolarization of 2–4 mV accompanied the isoprenaline‐induced decrease in volume. In the remaining five cells, neither an obvious isoprenaline‐induced decrease in volume nor membrane depolarization was observed. Under ruptured whole‐cell voltage clamp conditions, the activation of inward isoprenaline‐induced Cl− current decreased cell width.4. Cell width was seen to either decrease or increase when a large outward or inward K+ current, respectively, was induced by shifting the holding potential or by applying 200 μmol/L pinacidil. Under gramicidin‐perforated whole‐cell clamp conditions, the cell width did not change, even when a large inward K+ current was induced.5. When the test solution was applied to half of an elongated myocyte by using a micropipette, the cell width increased or decreased in the part exposed to the hypotonic or hypertonic test solutions, respectively. In contrast, in the other half of the elongated myocyte, the cell width responded in the opposite direction.6. It is concluded that a continuous ionic flux through ion channels is capable of inducing changes in cell volume by generating a localized osmotic gradient across the cardiac sarcolemma.
NBPA: A CEREBRAL ISCHAEMIC PROTECTIVE AGENT
Authors: Zhang JUNTIAN , Peng XINQI , Wei GUO , Su DAN 
Published: March 2003

SUMMARY1. NBPA is a derivative of 3‐n‐butylpathalide isolated from Apium granolens Linn.2. At concentrations ranging from 6 × 10–6 to 10–6 mol/L, NBPA inhibited the L‐type calcium current in guinea‐pig myocardial cells and cultured human neuroblastoma cells.3. At 10–6 mol/L, NBPA markedly inhibited calcium‐ dependent and ‐independent release of glutamate from synaptosomes.4. The [31P] nuclear magnetic resonance spectrum has shown that pretreatment with NBPA at 15 mg/kg, i.p., improved energy metabolism.5. In situ hybridization has shown that 10 and 20 mg/kg, i.p., NBPA prior to cerebral artery occlusion can accelerate the expression of heat shock protein 70 mRNA and inhibit c‐fos mRNA expression.6. It has been shown that NBPA decreases the nitric oxide content and bc nitric oxide synthase (NOS) activity in the global cerebral ischaemia–reperfusion model in rats. In addition, it has been shown that NBPA significantly inhibits the expression of inducible NOS protein.
ENDOTHELIN AND THE CENTRAL AND PERIPHERAL NERVOUS SYSTEMS: A DECADE OF ENDOTHELIN RESEARCH
Authors: Mortensen Luke H 
Published: March 2003

SUMMARY1. During the past decade, extensive investigation of the endothelin (ET) system, primarily characterized by its potent vasoactive peptide element ET‐1, has suggested a prominent role for this humoral agent and its isopeptides in cardiovascular and neural regulation.2. Major elements of this system, including its peptide isoforms, converting enzymes involved in their formation and metabolism, as well as multiple receptor subtypes, have been localized within various components of the cardiovascular system and the central and peripheral nervous systems.3. An understanding of the possible roles for the ET system in neural regulation and development has progressed over the past several years; most notable is the influence of ET on the central control of cardiovascular function and sympathetic tone.4. The present concentrated review of ET and the central and peripheral nervous systems is presented to introduce the other papers within this symposium by briefly describing the presence and influence of components of this unique peptide system within pertinent physiological structures involved in cardiovascular, adrenal, sympathetic and enteric developmental function.
ENDOTHELIN AND THE DEVELOPMENT OF THE ENTERIC NERVOUS SYSTEM
Authors: Gershon Michael D 
Published: March 2003

SUMMARY1. The enteric nervous system (ENS) is derived from cells that migrate to the bowel from the neural crest. These émigrés must find the gut, reach their correct locations within its wall and finally differentiate as neurons or glia.2. Because the crest‐derived precursor population is multipotent when it colonizes the bowel, the enteric micro‐environment plays a prominent role in ENS development.3. A number of molecules of the enteric micro‐environment have been found to promote the development of neurons.4. However, endothelin (ET)‐3 appears to be different from any of these in that its role appears to be to prevent premature neuronal differentiation.5. By activating ETB receptors, ET‐3 inhibits the differentiation of crest‐derived cells into neurons and promotes the development of smooth muscle.6. The effect of ET‐3 on smooth muscle down‐regulates the secretion of laminin‐1, which is a promoter of the formation of neurons.7. In the absence of ET‐3/ETB, crest‐derived cells develop as neurons and, thus, cease migrating before they complete the colonization of the bowel. This premature development leaves the terminal colon aganglionic.
Anti‐remodelling drugs for the treatment of asthma: requirement for animal models of airway wall remodelling
Authors: Fernandes Darren J , Xu Kai‐Feng , Stewart Alastair G 
Published: March 2003

SUMMARY1. Airway wall remodelling (AWR), the structural change induced by acute and chronic inflammation in the airways, may be one of the most significant and difficult to reverse components of progressive asthma.2. The mechanisms underlying the development of AWR are not known. Studies of only the most superficial wall structures of large airways can be conducted in living humans because of the degree of invasiveness required to measure airway structural changes. These studies reveal that currently available agents do not fully prevent or reverse AWR. Thus, animal models of asthma pathology may be used to assess the contribution of particular mediators and cells to the development of remodelling and may also prove to be useful in the initial screening of potential anti‐remodelling agents.3. Airway hyperresponsiveness and AWR stimulated by chronic antigen challenge in previously disease‐free animals is the most popular of the currently used models of remodelling. Other animal models include the use of specially bred strains with intrinsic airway hyperresponsiveness or animals that have a naturally occurring asthma‐like disease, such as cats with feline asthma or horses with heaves. The further development of animal models of AWR will facilitate the development of novel anti‐asthma therapies.
Sodium Sensitivity And Sympathetic Nervous System In Hypertension Induced By Long‐Term Nitric Oxide Blockade In Rats
Authors: Yuasa Shigekazu , Li Xiuping , Hitomi Hirofumi , Hashimoto Mayuko , Fujioka Hiroshi , Kiyomoto Hideyasu , Uchida Kouichi , Shoji Tetsuo , Takahashi Norihiro , Miki Shigehiro , Miyatake Akira , Mizushige Katsufumi , Matsuo Hirohide 
Published: March 2003

SUMMARY1. Pharmacological inhibition of nitric oxide (NO) synthesis is known to produce acute and chronic hypertension in many animal species, but the underlying mechanisms mediating the hypertension are not completely understood. In particular, the pathogenetic roles of sodium sensitivity and the sympathetic nervous system in this model of hypertension are controversial. The present study was designed to test the hypothesis that long‐term administration of the NO synthesis inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME) to male Sprague‐Dawley rats would produce a sodium‐sensitive hypertension and that the enhanced activity of the sympathetic nervous system in this type of hypertension contributes to the sodium sensitivity.2. NG‐Nitro‐L‐arginine methyl ester was added to drinking fluid for 8 weeks at a concentration of 16 mg/dL. Rats received tap water for the first 4 weeks of the study and were then divided into two groups and placed on either a normal or high sodium intake (ingestion of either tap water or 0.9% NaCl, respectively). Awake systolic blood pressure was measured by the tail‐cuff method every week. Urinary excretion rates of the stable NO metabolites and catecholamines during NO synthesis inhibition were examined.3. Long‐term administration of L‐NAME produced a marked and sustained elevation in arterial pressure without altering urine flow, or sodium excretion rate. NG‐Nitro‐L‐arginine methyl ester‐induced hypertension was accompanied by a decreased urinary excretion of the stable NO metabolites NO2– and NO3– and was aggravated when rats drank 0.9% NaCl in place of tap water. Urinary excretion of adrenaline and noradrenaline, but not dopamine, in L‐NAME‐treated rats increased significantly within the first week of the study compared with control rats. L‐Arginine (2 g/dL in drinking fluid) completely reversed the elevation of arterial pressure as well as the decrease in urinary NO2– and NO3– excretion and the increased urinary excretion of catecholamines associated with L‐NAME treatment by 3 weeks of concomitant administration.4. These results suggest that long‐term inhibition of NO synthesis produces a sodium‐sensitive hypertension and that changes in sympathetic nerve activity may, at least in part, contribute to the sodium sensitivity in this type of hypertension.
Contribution Of Nitric Oxide, Cyclic Gmp And K+ Channels To Acetylcholine‐Induced Dilatation Of Rat Conduit And Resistance Arteries
Authors: Woodman Owen L , Wongsawatkul Orapin , Sobey Christopher G 
Published: March 2003

SUMMARY1. We compared the effects of inhibiting nitric oxide synthase (NOS), soluble guanylate cyclase (sGC) and K+ channel activation on dilator responses to acetylcholine (ACh) in rat resistance (hindquarters) and conduit arteries (thoracic aorta).2. In rat perfused hindquarters, the NO synthase inhibitor Nω‐nitro‐L‐arginine (L‐NNA; 1 mmol/L) partially inhibited the ACh‐induced dilatation and the combination of L‐NNA + haemoglobin (Hb; 20 μmol/L), a NO scavenger, did not further affect the response. Exposure to high K+ (30 mmol/L) also inhibited the response to ACh and this response was further reduced by L‐NNA + high K+. Surprisingly, when applied alone 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ), an inhibitor of sGC, did not affect responses to ACh, whereas treatment with ODQ + high K+ markedly impaired dilatation.3. In aortic rings precontracted with phenylephrine (PE; 0.01–1 μmol/L), the maximum relaxation to ACh was significantly reduced by L‐NNA (0.1 mmol/L) and further inhibited by L‐NNA + Hb (20 μmol/L). At 10 μmol/L, ODQ alone inhibited the maximum relaxation to ACh, which was further reduced by ODQ + high K+ (30 mmol/L). High K+ caused a smaller but significant inhibition of ACh‐induced relaxation.4. These results suggest that NO and cGMP play a relatively greater role in ACh‐induced dilatation of the aorta compared with the hindquarters resistance vasculature and are consistent with the hypothesis that a non‐NO endothelium‐derived hyperpolarizing factor (endothelium‐derived hyperpolarizing factor; EDHF) makes a relatively greater contribution to dilatation of resistance vessels than in conduit arteries. The data suggest that when sGC is inhibited, a compensatory mechanism involving K+ channel opening by NO can largely maintain ACh‐induced vasodilator responses of resistance vessels. Furthermore, when NO synthesis is blocked, a non‐ NO EDHF may play a role in ACh‐induced dilatation of the resistance vasculature.
Formation Of The Aqueous Humor
Authors: Macknight Anthony Dc , McLaughlin Charles W , Peart David , Purves Robert D , Carré David A , Civan Mortimer M 
Published: March 2003

SUMMARY1. Glaucoma is a worldwide disease affecting approximately 1–2% of the population aged over 35 years in industrial countries and is a major cause of blindness.2. Glaucoma is usually associated with an increased intra‐ocular pressure reflecting an imbalance between the rate of production of fluid (the aqueous humor) by the ciliary epithelial cells and its drainage from the eye. Therefore, it is important to understand how this secretion is produced. This requires a knowledge of ciliary epithelial cell composition, which has, in the past, proved difficult to obtain in mammalian preparations.3. We have recently used the technique of electron‐probe X‐ray microanalysis to determine this composition under a variety of in vitro conditions.4. Our results have led to a new model for this secretion that emphasizes the potential secretory role of the Na+/K+/2Cl– cotransporter.
Nitric Oxide Production And Hepatic Dysfunction In Patients With Postoperative Sepsis
Authors: Satoi Sohei , Kamiyama Yasuo , Kitade Hiroaki , Kwon A‐Hon , Takahashi Kanji , Wei Tu , Inoue Tomohisa , Takahashi Hakuo 
Published: March 2003

SUMMARY1. Although hepatic function is well known to deteriorate following bacterial infection, the underlying mechanisms remain poorly understood. We have previously reported that nitric oxide (NO) radical leads to a decrease in the ketone body ratio (KBR) and in ATP content due to the inhibition of mitochondrial electron transport in primary cultured rat hepatocytes.2. To evaluate the effects of NO radical on the liver in patients with postoperative sepsis, we analysed both the stable end‐product of nitric oxide radical (NOx) as well as the arterial KBR (AKBR), which reflects liver tissue NAD+/NADH.3. Twenty patients who had undergone general abdominal surgery and who developed postoperative sepsis were divided into two groups: (i) surviving; and (ii) non‐surviving. Blood samples were collected before the development of postoperative sepsis and every 3 days until the patient either died or was discharged from hospital.4. Plasma NOx levels in seven patients who subsequently died became progressively higher than those in the 13 surviving patients over the clinical course of postoperative sepsis.5. In the non‐surviving group, the AKBR was significantly lower than in surviving patients, indicating impaired hepatic function. In contrast, plasma NOx levels in non‐surviving patients were significantly higher than in surviving patients.6. Decreases in AKBR to levels below 0.7 in non‐surviving patients followed high NOx levels. Moreover, plasma NOx levels were closely correlated with the AKBR, indicating that NO radical is associated with mitochondrial dysfunction in the liver.7. It is likely that the overproduction of NO radical plays an important role in causing fatal metabolic disorders in patients with postoperative sepsis.
Cardiac And Vascular Responses In Deoxycorticosterone Acetate‐Salt Hypertensive Rats
Authors: Brown Lindsay , Ooi Sze‐Yuan , Lau Kevin , Sernia Conrad 
Published: March 2003

SUMMARY1. Hypertension leads to ventricular hypertrophy and, eventually, to heart failure. The present study has investigated the functional consequences of deoxycorticosterone acetate (DOCA)‐salt hypertension in rats by defining the inotropic, chronotropic and vascular responses to noradrenaline (NA; β1‐adrenoceptor agonist), forskolin (adenylate cyclase activator) and theophylline (phosphodiesterase inhibitor).2. Administration of DOCA (25 mg, s.c., every 4th day) and excess salt (1% NaCl in drinking water) to uninephrectomized rats increased left ventricular wet weight by 35 and 71% after 4 and 8 weeks, respectively. Addition of KCl (0.4%) or CaCl2 (1%) in the drinking water for 4 weeks attenuated blood pressure increases, but not ventricular weight increases (46 and 28%, respectively).3. Positive inotropic responses in papillary muscles from uninephrectomized rats to NA (–log EC50 6.73±0.38; n = 7), forskolin (–log EC50 6.15±0.31; n = 7) and CaCl2 (–log EC50 2.40±0.02; n = 14) were unchanged in hypertrophied left ventricles of DOCA and DOCA‐CaCl2 rats, although maximal responses to NA were decreased in DOCA‐KCl rats (1.2±0.6 mN, n = 8; DOCA‐salt 2.9±0.5 mN, n = 6); theophylline was less potent in DOCA‐salt rats. Positive chronotropic responses to NA, forskolin and theophylline in right atria and negative inotropic responses to carbachol in papillary muscles were unchanged.4. Maximal vasoconstrictor responses to NA in thoracic aortic rings were reduced in DOCA‐KCl rats to 2.4±0.9 mN (n = 5), but were increased in DOCA‐CaCl2 rats to 26.6±2.2 mN (n = 7; DOCA‐salt 7.8±2.2 mN, n = 9). Vasorelaxant responses to forskolin and theophylline were unchanged.5. These results show that cardiac responses are only minimally affected during the development of DOCA‐salt hypertension‐induced hypertrophy, despite the reported decreases in adenylate cyclase activity, in these rats. This is in contrast with the decreased responses reported in other rat models of cardiac hypertrophy and in the failing human heart. Thus, hypertrophy in hearts of DOCA‐salt hypertensive rats does not produce similar changes to the failing human heart.
Beneficial Effects Of Fish Oil On Glucose Metabolism In Spontaneously Hypertensive Rats
Authors: Ajiro Koji , Sawamura Makoto , Ikeda Katsumi , Nara Yasuo , Nishimura Masayoshi , Ishida Hitoshi , Seino Yutaka , Yamori Yukio 
Published: March 2003

SUMMARY1. Increased interest in fish oil led us to examine their metabolic effects in spontaneously hypertensive rats, which have been reported to have glucose intolerance.2. Rats were divided into three groups: (i) a control group fed standard rat laboratory chow; (ii) a lard group fed a high‐fat diet containing 20% lard; and (iii) a fish oil group fed a high‐fat diet containing 20% fish oil for 14 weeks.3. Systolic blood pressure and fasting blood glucose were markedly increased in the lard group, whereas in the fish oil group they were only transiently increased at the beginning and decreased to levels seen in the control group.4. Intraperitoneal glucose tolerance test demonstrated that fish oil reversed the impairment of glucose disposal found in the lard group. However, plasma insulin levels were raised transiently at 30 min in the fish oil group compared with the control group.5. Insulin secretion from pancreatic islets stimulated with glucose in vitro was also enhanced by fish oil.6. These results lead us to conclude that fish oil improves glucose tolerance by enhancing insulin secretion from pancreatic β‐cells.
Tonic Potentiation And Attenuation Produced By Membrane Depolarization In Guinea‐Pig Trachealis
Authors: Yamaki Kenichi , Ogawa Masahiro , Ito Yasushi 
Published: March 2003

SUMMARY1. We studied how membrane depolarization directly affected intracellular Ca2+ signalling when voltage‐operated Ca2+ channels (VOCC) were not available in guinea‐pig tracheal smooth muscle. To block VOCC, we used 3 μmol/L verapamil, which completely abolished high K+ (20–60 mmol/L)‐induced contraction, and elevation of fura‐2 signal.2. Muscle tone was generated by adding Ca2+ to the extracellular Ca2+‐free solution containing prostaglandin (PG)E2 (100 nmol/L) after abolishing basal tone with indomethacin (1 μmol/L).3. In the absence of verapamil, high K+ (20–60 mmol/L) solution potentiated 2.4 mmol/L Ca2+‐induced sustained contractions. Even in the presence of 3 μmol/L verapamil, replacement with 20 and 40 mmol/L K+ solution induced tonic potentiation, which was changed to attenuation with a higher K+ solution (60 mmol/L), lower extracellular Ca2+ concentration ([Ca2+]o) and pretreatment with cyclopiazonic acid (10 μmol/L), a Ca2+ sequestration inhibitor.4. These results indicate that the balance between depolarization‐dependent Ca2+ release and receptor‐operated cation channel inhibition may determine whether tonic potentiation or attenuation is manifested, depending on the availability of VOCC, the magnitude of the depolarization, [Ca2+]o and Ca2+ content in the sarcoplasmic reticulum.