bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role Of Protein Kinase C In Myogenic Calcium– Contraction Coupling Of Rat Cannulated Mesenteric Small Arteries
Authors: Wesselman Jos Pm , Spaan Jos AE , Meulen Esther T van der , VanBavel Ed 
Published: March 2003

SUMMARY1. The present study was designed to determine the role of protein kinase C (PKC) in the myogenic response of small arteries. In particular, we tested whether inhibition of PKC reverses the previously found pressure‐induced elevation of contractile element calcium sensitivity.2. Rat mesenteric small arteries were cannulated and pressurized. The internal diameter was continuously monitored with a video camera and intracellular calcium levels were measured by means of fura‐2. Myogenic responses were observed when the pressure was raised stepwise from 20 to 60 and then to 100 mmHg in physiological saline solution and during application of phenylephrine (0.1 or 1 μmol/L) or potassium (36 mmol/L).3. The PKC inhibitors H‐7 (20 μmol/L), staurosporine (100 nmol/L) and calphostin C (10 nmol/L) all completely abolished the myogenic response. Whereas staurosporine caused an ongoing reduction in intracellular calcium, pressure‐induced calcium transients were not affected by either H‐7 or calphostin C. In particular, the slope of the wall tension–calcium relationship remained similar in the presence of both H‐7 and calphostin C, despite an upward shift of this relationship to higher calcium levels in the case of calphostin C.4. These results show that activity of PKC isoform(s) is essential for myogenic calcium–contraction coupling.
Cerebrovascular Dysfunction After Subarachnoid Haemorrhage: Novel Mechanisms And Directions For Therapy
Authors: Sobey Christopher G 
Published: March 2003

SUMMARY1. When a cerebral aneurysm ruptures, bleeding and clot formation occur around the surface of the brain, including several major blood vessels. The resulting condition, known as subarachnoid haemorrhage (SAH), often results in death or severe disability and is a significant cause of stroke. Delayed cerebral vasospasm and impaired vasodilatation are critical clinical complications that occur after SAH. Mechanisms contributing to the development of vasospasm and abnormal reactivity of cerebral arteries after SAH have been intensively investigated in recent years. The present short review briefly decribes recent advances in our knowledge of two relatively novel aspects of the mechanism(s) underlying the vascular abnormalities following SAH.2. Cerebral arteries are depolarized after SAH, possibly due to decreased activity of potassium channels in vascular muscle. Decreased basal activation of potassium channels may be due to several mechanisms, including impaired activity of nitric oxide (NO). Vasodilator drugs that produce hyperpolarization, such as potassium channel openers, appear to be particularly effective for dilating cerebral arteries after experimental SAH.3. Subarachnoid haemorrhage often involves decreased responsiveness of cerebral arteries to NO. This could be due to impaired activity of soluble guanylate cyclase, resulting in reduced basal levels of cGMP in cerebral vessels. However, an alternative explanation is that there may be an increased rate of cGMP hydrolysis by phosphodiesterase (PDE)‐V in the cerebral vascular wall and that this abnormality contributes substantially to the impairment of NO‐mediated cerebral vasodilatation after SAH. In support of this proposal, vasodilator responses to NO are reported to be normalized when coadministered with a PDE‐V inhibitor following experimental SAH.4. Thus, in cerebral vascular muscle after SAH, abnormalities of vasodilator mechanisms involving potassium channel function and also NO/cGMP activity may contribute to cerebral vascular dysfunction. These mechanisms may also represent useful and novel therapeutic targets for the treatment of vasospasm.
A Hypothesis About A Mechanism For The Programming Of Blood Pressure And Vascular Disease In Early Life
Authors: Martyn Cn , Greenwald Se 
Published: March 2003

SUMMARY1. There is now a great deal of evidence that people whose weight at birth was low tend to have higher blood pressure and increased risk of death from cardiovascular disease as adults.2. We argue that, in fetuses whose growth is impaired, synthesis of elastin in the walls of the aorta and large arteries is deficient and that this deficiency leads to permanent changes in the mechanical properties of these vessels.3. Over a lifetime, such changes could predispose an individual to higher blood pressure and cardiovascular disease.
Sympathetic Nerve Biology In Essential Hypertension
Authors: Esler Murray , Rumantir Magdalena , Kaye David , Jennings Garry , Hastings Jacqui , Socratous Flora , Lambert Gavin 
Published: March 2003

SUMMARY1. Although the importance of sympathetic nervous activation in the pathogenesis of essential hypertension is well documented, the exact pathophysiology of the sympathetic nervous dysfunction present remains to be delineated. There are several possible explanations for the increased spillover of noradrenaline from the kidneys and heart to plasma, a key piece of evidence supporting the neurogenic basis of essential hypertension, in addition to the obvious one of an increased rate of sympathetic nerve firing.2. The possibility that there may be an increase in the density of sympathetic innervation in human hypertension, well documented in the spontaneously hypertensive rat, is currently under investigation by us.3. Adrenaline cotransmission is present in the cardiac sympathetic nerves of patients with essential hypertension, presumptive evidence of their exposure to high levels of stress and a possible basis for the observed increase in cardiac noradrenaline spillover, through presynaptic augmentation of noradrenaline release.4. Phenotypic evidence exists also of faulty noradrenaline reuptake into the sympathetic nerves of the heart in essential hypertension, an abnormality that would amplify the sympathetic neural signal by impairing removal of noradrenaline from the synaptic cleft.
New Elements In Human Renin Promoter Involved In Cell‐Specific Expression
Authors: Germain Stéphane , Fuchs Sébastien , Philippe Josette , Corvol Pierre , Pinet Florence 
Published: March 2003

SUMMARY1. The renin–angiotensin system plays a major role in blood pressure regulation and electrolyte homeostasis through the action of angiotensin (Ang) II. The first and rate‐limiting step in the production of AngII is the conversion of angiotensinogen into AngI, which is catalysed by the aspartyl protease renin (EC 3.4.23.15). Circulating active renin is mainly synthesized, processed and secreted by the juxtaglomerular cells within the kidney.2. To determine the renin 5′‐flanking sequences involved in cell and tissue specificity, ex vivo and in vivo studies were performed. Several constructs of various lengths of renin promoter linked to the luciferase gene were first tested ex vivo by transfection in primary cultures of human chorionic cells. The constructs giving a high and specific expression in renin‐producing cells were then tested in vivo in a transgenic mice model.3. The reporter gene chosen to generate transgenic mice was LacZ and the screening was performed in embryos at the embryonic day (E) 15 stage, at which mouse renin is expressed in the developping vessels of the kidney.4. Only constructs containing more than 5.7 kb of the human renin promoter lead to specific expression of β‐galactosidase in the kidney.5. Our results demonstrate that the human renin distal promoter region allows a more restricted expression of LacZ in the renin‐expressing cells in transgenic mice.
Paring Down On Descartes: A Review Of Brain Noradrenaline And Sympathetic Nervous Function
Authors: Lambert Gavin W 
Published: March 2003

SUMMARY1. The conceptual framework of mind–body interaction can be traced back to the seminal observations of the French philosopher and mathematician René Descartes (1596–1650). Descartes succeeded in eliminating the soul’s apparent physiological role and established the brain as the body’s control centre.2. While the pivotal role played by the central nervous system (CNS) in the maintenance of physiological and psychological health has long been recognized, the development of methods designed for the direct examination of human CNS processes has only recently come to fruition.3. There exists a substantial body of evidence derived from clinical and experimental studies indicating that CNS monoaminergic cell groups, in particular those using noradrenaline as their neurotransmitter, participate in the excitatory regulation of the sympathetic nervous system and the development and maintenance of the hypertensive state.4. In essential hypertension, particularly in younger patients, there occurs an activation of sympathetic nervous outflows to the kidneys, heart and skeletal muscle. The existence of a correlation between subcortical brain noradrenaline turnover and total body noradrenaline spillover to plasma, resting blood pressure and heart rate provides further support for the observation that elevated subcortical noradrenergic activity subserves a sympathoexcitatory role in the regulation of sympathetic preganglionic neurons of the thorocolumbar cord.
‘Slow Pressor’ Hypertension From Low‐Dose Chronic Angiotensin II Infusion
Authors: Edgley AJ , Kett MM , Anderson WP 
Published: March 2003

SUMMARY1. Angiotensin (Ang) II causes growth‐related effects on vascular smooth muscle cells in vitro and in vivo.2. Chronic infusions of AngII systemically, at doses that are initially subpressor, result in slowly progressive increases in arterial pressure (‘slow‐pressor’ hypertension). It has been suggested that the hypertension is due to induced growth in systemic resistance vessel walls by the AngII infusions.3. We report the results of several studies investigating whether there are also induced structural changes in renal resistance vessels during chronic AngII infusions. We have developed models in Sprague‐Dawley rats in which low‐dose AngII infusions, either into the renal artery (thus restricting the effects to the kidney) or systemically, result in hypertension.5. In both models, we have evidence suggesting that chronic AngII infusions have resulted in apparent structurally induced reductions in renal vasculature lumen upstream to the glomerulus.6. The role of these renal changes in the development of the hypertension remain to be determined.
Exercise And Skeletal Muscle Gene Expression
Authors: Cameron‐Smith David 
Published: March 2003

SUMMARY1. Skeletal muscle is a complex and heterogenous tissue capable of remarkable adaptation in response to exercise training. The role of gene transcription, as an initial target to control protein synthesis, is poorly understood.2. Mature myofibres contain several hundred nuclei, all of which maintain transcriptional competency, although the localized responsiveness of nuclei is not well known. Myofibres are capable of hypertrophy. These processes require the activation and myogenic differentiation of mononuclear satellite cells that fuse with the enlarging or repairing myofibre.3. A single bout of exercise in human subjects is capable of activating the expression of many diverse groups of genes.4. The impact of repeated exercise bouts, typical of exercise training, on gene expression has yet to receive systematic investigation.5. The molecular programme elicited by resistance exercise and endurance exercise differs markedly. Muscular hypertrophy following resistance exercise is dependent on the activation of satellite cells and their subsequent myogenic maturation. Endurance exercise requires the simultaneous activation of mitochondrial and nuclear genes to enable mitochondrial biogenesis.6. Future analysis of the regulation of genes by exercise may combine high‐throughput technologies, such as gene‐chips, enabling the rapid detection and analysis of changes in the expression of many thousands of genes.
Mitochondrial Proteins In Hypertrophy And Atrophy: A Transcript Analysis In Rat Heart
Authors: Taegtmeyer Heinrich , Razeghi Peter , Young Martin E 
Published: March 2003

SUMMARY1. Metabolic processes are acutely and chronically regulated in response to changes in the workload of the heart. Acute changes in cardiac work result in activation and inactivation of existing enzymes and in altered fluxes through existing metabolic pathways. Sustained or chronic changes in cardiac work result in both trophic and transcriptional alterations.2. The metabolic consequences of a sustained increase or decrease in the workload of the heart are surprisingly uniform and consist of a switch from the predominant oxidation of fatty acids to oxidation of glucose.3. This switch is reflected in the changes of the transcript levels of three key regulators of mitochondrial function: pyruvate dehydrogenase kinase 4 (PDK4), which phosphorylates and inactivates the pyruvate dehydrogenase complex, malonyl‐CoA decarboxylase (MCD), which regulates malonyl‐CoA levels and, therefore, rates of β‐oxidation of long‐chain fatty acids, and uncoupling protein 3 (UCP‐3), which uncouples the oxidative phosphorylation of ADP.4. The transcript levels of all three proteins are downregulated in hypertrophy as well as in atrophy of rat heart. All three transcripts are transcriptionally regulated by the nuclear receptor peroxisome proliferator‐activated receptor α
(PPARα).5. Diminished expression of PPARα and PPARα‐regulated
genes constitutes an adaptive mechanism in response to altered workload, because
reactivation of PPARα in hypertrophied heart results in severe contractile dysfunction.
Glutamate Circuits In Selected Medullo‐Spinal Areas Regulating Cardiovascular Function
Authors: Sapru HN 
Published: March 2003

SUMMARY1. The importance of the medullo‐spinal neuronal pools in the regulation of cardiovascular function has been known for a long time. However, important groups of these neurons, interconnections between them and the neurotransmitters released at their projections have been identified with certainty only during the past two decades.2. Some of the medullo‐spinal neuronal pools mediating cardiovascular function include the nucleus tractus solitarius, caudal ventrolateral medullary depressor area, rostral ventrolateral medullary pressor area, nucleus ambiguus and intermediolateral cell column of the thoracolumbar spinal cord. Interactions between these selected neuronal groups and neurotransmitters in the pathways connecting them are discussed in the present short review.
Role Of Excitatory Amino Acid Inputs To The Rostral Ventrolateral Medulla In Cardiovascular Regulation
Authors: Sved Alan F , Ito Satoru , Yajima Yoshiharu 
Published: March 2003

SUMMARY1. Excitatory amino acid (EAA)‐mediated neural transmission in the rostral ventrolateral medulla (RVLM) is important for many cardiovascular reflexes, although the receptor subtypes involved vary depending on the specific response.2. Although injection of the EAA ionotropic receptor antagonist kynurenic acid into the RVLM has no effect on baseline arterial pressure, this lack of effect appears to result from EAA inputs to RVLM exciting both excitatory and inhibitory mechanisms within the RVLM.3. The balance between EAA‐mediated excitation and inhibition of RVLM neurons may be shifted to excitation in experimental models of hypertension.4. The excitatory influence that EAA inputs to the RVLM have on vasomotor neurons in the RVLM may involve a sarthran‐sensitive intermediary in the RVLM.
Beneficial Effect Of T‐1095, A Selective Inhibitor Of Renal Na+–Glucose Cotransporters, On Metabolic Index And Insulin Secretion In Spontaneously Diabetic Gk Rats
Authors: Nunoi Kumiko , Yasuda Koichiro , Adachi Tetsuya , Okamoto Yoshimasa , Shihara Nobuyuki , Uno Mika , Tamon Akiko , Suzuki Naoko , Oku Akira , Tsuda Kinsuke 
Published: March 2003

SUMMARY1. To investigate the pharmacological effects of T‐1095, this novel derivative of phlorizin was administered to GK rats for 8 weeks. T‐1095 treatment significantly lowered plasma glucose and glycosylated haemoglobin (HbA1c) levels, but did not significantly affect bodyweight.2. T‐1095 treatment did not affect 3.3 mmol/L glucose‐induced insulin secretion in the isolated perfused pancreas of GK rats.3. The peak insulin release in T‐1095‐treated GK rats was significantly higher during the first phase than in untreated GK rats (3–4 min after beginning 16.7 mmol/L glucose perfusion). The total amount of insulin secreted during the first phase in T‐1095‐treated GK rats was significantly higher than in untreated GK rats (35.3 ± 1.4 vs 27.3 ± 2.5 ng in T‐1095‐treated compared with untreated rats, respectively).4. During the second phase, insulin release in T‐1095‐treated GK rats was somewhat higher than in untreated GK rats (7–30 min after beginning 16.7 mmol/L glucose perfusion). The total amount of insulin secreted during the second phase in T‐1095‐treated GK rats was significantly higher than in untreated GK rats (88.2 ± 6.1 vs 68.1 ± 5.7 ng, respectively).5. The total amount of insulin secreted during perfusion in T‐1095‐treated GK rats was significantly higher than in untreated GK rats (123.5 ± 7.3 vs 95.4 ± 7.7 ng, respectively).6. These data show that the metabolic indices, plasma glucose and HbA1c levels and insulin secretion are significantly improved by T‐1095 treatment in GK rats, which are spontaneously diabetic rats, suggesting its usefulness as a novel oral therapeutic antidiabetic agent.
Endothelial Function In Mesenteric Resistance Arteries From The Genetically Hypertensive Rat
Authors: Liu Hanzhong , Ledingham Janet M , Mullaney Ian , Laverty Richard 
Published: March 2003

SUMMARY1. Endothelial function in mesenteric resistance arteries (MRA) from male 12‐week‐old New Zealand genetically hypertensive (GH) rats and their normotensive control strain (N) was compared in vessels mounted on a wire myograph and by the production of intracellular cGMP. In parallel experiments, MRA from the spontaneously hypertensive (SHR) rat strain, in which there is an endothelial defect, and from GH rats, in which an endothelial defect was induced by chronic nitric oxide synthase (NOS) inhibition with Nω‐nitro‐L‐arginine methyl ester (L‐NAME), were studied.2. Contractile responses to potassium (124 mmol/L) depolarization and to NA (10–8 to 10–4 mol/L) were similar in GH and N rats; however, in SHR, enhanced contractile responses were found (P < 0.05). The endothelium‐dependent relaxation induced by acetylcholine (ACh; 10–9 to 10–4 mol/L) and endothelium‐ independent relaxation induced by sodium nitroprusside (SNP; 10–9 to 10–4 mol/L) were identical in preparations from GH and N. A significantly attenuated (P < 0.01) vasodilator response to ACh was observed in preparations from SHR.3. Levels of intracellular cGMP were similar in untreated small mesenteric arterial trees from GH, N and SHR rats. Acetylcholine (10–5 mol/L) significantly (P < 0.001) increased the cGMP content in both GH and N rats. A non‐significant increase occurred in cGMP content in preparations from SHR.4. In GH rats given L‐NAME (10 mg/kg per day for up to 5 weeks), an attenuated (P < 0.01) endothelium‐dependent relaxation to ACh and an enhanced (P < 0.01) endothelium‐ independent relaxation to SNP were observed. Lower basal cGMP levels were found in preparations from L‐NAME‐treated GH rats and ACh (10–5 mol/L) failed to significantly elevate the cGMP content in these preparations.5. These experiments failed to show evidence of reduced endothelial function in GH rats, although an endothelial defect in SHR rats and after NOS inhibition in GH rats could be demonstrated.
Smooth Muscle And Endothelial Function Of Arterial Grafts For Coronary Artery Bypass Surgery
Authors: He Guo‐Wei , Yang Qin , Yang Cheng‐Qin 
Published: March 2003

SUMMARY1. Various small/mid‐sized conductance arteries have been used for coronary artery bypass grafting as arterial grafts, but unanimous opinion to the best use of these grafts has not been formed.2. Arterial grafts are not uniform in their biological characteristics.3. The differences among the arteries may involve the contractility of the vessel. Based on studies of the contractility of arterial grafts, a clinical classification was formed to describe the tendency of vasospasm in the arterial grafts.4. The differences among arterial grafts also involve endothelial function. This refers to both nitric oxide release from the endothelium, as well as endothelium‐derived hyperpolarizing factor‐mediated hyperpolarization and relaxation.5. The difference in the peri‐operative behaviour of the grafts and in their long‐term patency may be related to different characteristics. These should be taken into account in the use of arterial grafts, some of which are subject to more active pharmacological intervention during and after operation to obtain satisfactory results. The clinical choice of grafts must be based on the general condition of the patient, the biological characteristics of the graft, the anatomy of the coronary artery, the match between the coronary artery and the graft and the technical considerations, including antispastic management.
Contractile properties of the diaphragm in creatine‐fed rats
Authors: McGuire M , Bradford A , MacDermott M 
Published: March 2003

Summary1. Creatine feeding increases the oxidative capacity of type 1 skeletal muscle fibres and, in soleus muscles, consisting mainly of type 1 fibres, increases fatigue resistance. The diaphragm contains a relatively large content of type 1 fibres and respiratory muscle fatigue is a cause of respiratory failure. The aim of the present study was to determine whether creatine supplements increase fatigue resistance in the diaphragm.2. Rats were given creatine monohydrate (2.55 g/L) in the drinking water. After 5–6 days, isometric contractile properties were measured in strips of costal diaphragm in Krebs' solution at 30°C. Measurements were also made in soleus muscle strips. Values for strips from creatine‐fed rats were compared with those from control rats.3. Creatine feeding did not increase fatigue resistance and had no effect on twitch or tetanic tension or twitch kinetics in the diaphragm. Creatine increased fatigue resistance in soleus muscles, as reported previously.
Old and new risk factors for atherosclerosis and development of treatment recommendations
Authors: Frohlich Jiri , Lear Scott A 
Published: March 2003

Summary1. The development of atherosclerosis, including the role of the classical and new risk factors, is briefly reviewed an emphasis on the links between some of these risk factors and atherogenesis.2. While genetic factors are doubtlessly important, they contribute (from the population point of view) little to the overall burden of atherosclerosis.3. Our studies on the relationship between abdominal obesity and metabolic risk factors in two ethnic groups, namely individuals of Cantonese and European background, suggest that different ranges for at least some of the risk factors should be established for specific ethnic groups (e.g. waist circumference for individuals of Chinese and European background).4. Using the example of differences between Cantonese heterozygotes for familial hypercholesterolaemia living in Vancouver, Canada, and Canton, China, we demonstrate how the environment can modify a genetic predisposition for atherosclerosis.5. Gender differences are illustrated by a study of serum lipoprotein (a) as a risk factor in men and women.6. The principles of current Canadian recommendations for the assessment and treatment of atherosclerosis are outlined; they are based on knowledge gained from both basic and clinical research of atherosclerosis.