Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Cerebral vascular effects of reactive oxygen species: recent evidence for a role of NADPH-oxidase.","authors":"Tamara M Paravicini,&nbsp;Christopher G Sobey","doi":"10.1046/j.1440-1681.2003.03920.x","DOIUrl":"https://doi.org/10.1046/j.1440-1681.2003.03920.x","url":null,"abstract":"<p><p>1. Reactive oxygen species (ROS) are a diverse family of molecules that are produced throughout the vascular wall. Many ROS, such as the superoxide anion (*O2-) and hydrogen peroxide (H2O2), are now known to act as cellular signalling molecules within blood vessels. In particular, these molecules can exert powerful effects on vascular tone. 2. Cerebral arteries are relatively unusual in their responsiveness to ROS. Unlike in many systemic vessels, both *O2- and H2O2 can cause vasodilatation in the cerebral microcirculation. 3. Reactive oxygen species can be produced in the vasculature via a variety of mechanisms; however, it appears that the primary source of *O2- within blood vessels is the enzyme NADPH-oxidase. 4. In cerebral vessels, activation of NADPH-oxidase causes both *O2- production and vasodilatation, indicating that NADPH-oxidase-derived ROS may have a functional role in the regulation of cerebral vascular tone. 5. Elevated levels of NADPH-oxidase activity and expression occur in cardiovascular disease states such as hypertension, atherosclerosis and subarachnoid haemorrhage. 6. Thus, ROS may contribute to the regulation of cerebral vascular tone during both physiological and pathological conditions.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"30 11","pages":"855-9"},"PeriodicalIF":0.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1440-1681.2003.03920.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24127263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico insights: chemical and structural characteristics associated with uridine diphosphate-glucuronosyltransferase substrate selectivity.","authors":"P A Smith,&nbsp;M J Sorich,&nbsp;R A McKinnon,&nbsp;J O Miners","doi":"10.1046/j.1440-1681.2003.03923.x","DOIUrl":"https://doi.org/10.1046/j.1440-1681.2003.03923.x","url":null,"abstract":"<p><p>1. Undesirable absorption, distribution, metabolism, excretion properties are the cause of many drug development failures and this has led to the need to identify such problems earlier in the development process. This work highlights computational (in silico) approaches used to identify characteristics influencing the metabolism of uridine diphosphate (UDP)-glucuronosyltransferase (UGT) substrates. Uridine diphosphate-glucuronosyltransferase facilitates conjugation between glucuronic acid and a nucleophilic site within a substrate and is one of the major drug-metabolizing enzymes. 2. An understanding of the relevant structural and chemical characteristics of the ligand and the enzyme active site will lead to greater utilization of metabolically relevant structural information in drug design. However, an X-ray crystal structure of UGT is not yet available, little has been reported about important structurally or catalytically relevant amino acids and only recently has the reported substrate profile of UGT isoforms reached an interpretable level. 3. A database of all the known substrates and non-substrates for each human UGT isoform was assembled and a range of modelling approaches assessed. Currently, pharmacophore models developed using Catalyst (Accelrys, San Diego, CA, USA) indicate that substrates of the UGT1A family share two key hydrophobic regions 3 and 6-7 A from the site of glucuronidation in a well-defined spatial geometry. Furthermore, two-dimensional quantitative structure-activity relationship models show significant reliance on substrate lipophilicity and a range of other descriptors that are known to capture information relevant to ligand-protein interactions. 4. In conclusion, substrate-based modelling of UGT appears both useful and feasible, with significant potential for determining aspects of chemical structure associated with metabolism and to quantify the nature of the relationship for UGT substrates. The development of a novel, user-defined 'glucuronidation feature' for alignment was crucial to the development of pharmacophore-based UGT models.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"30 11","pages":"836-40"},"PeriodicalIF":0.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1440-1681.2003.03923.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24127259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric oxide, human diseases and the herbal products that affect the nitric oxide signalling pathway.","authors":"Francis I Achike,&nbsp;Chiu-Yin Kwan","doi":"10.1046/j.1440-1681.2003.03885.x","DOIUrl":"https://doi.org/10.1046/j.1440-1681.2003.03885.x","url":null,"abstract":"<p><p>1. Nitric oxide (NO) is formed enzymatically from l-arginine in the presence of nitric oxide synthase (NOS). Nitric oxide is generated constitutively in endothelial cells via sheer stress and blood-borne substances. Nitric oxide is also generated constitutively in neuronal cells and serves as a neurotransmitter and neuromodulator in non-adrenergic, non-cholinergic nerve endings. Furthermore, NO can also be formed via enzyme induction in many tissues in the presence of cytokines. 2. The ubiquitous presence of NO in the living body suggests that NO plays an important role in the maintenance of health. Being a free radical with vasodilatory properties, NO exerts dual effects on tissues and cells in various biological systems. At low concentrations, NO can dilate the blood vessels and improve the circulation, but at high concentrations it can cause circulatory shock and induce cell death. Thus, diseases can arise in the presence of the extreme ends of the physiological concentrations of NO. 3. The NO signalling pathway has, in recent years, become a target for new drug development. The high level of flavonoids, catechins, tannins and other polyphenolic compounds present in vegetables, fruits, soy, tea and even red wine (from grapes) is believed to contribute to their beneficial health effects. Some of these compounds induce NO formation from the endothelial cells to improve circulation and some suppress the induction of inducible NOS in inflammation and infection. 4. Many botanical medicinal herbs and drugs derived from these herbs have been shown to have effects on the NO signalling pathway. For example, the saponins from ginseng, ginsenosides, have been shown to relax blood vessels (probably contributing to the antifatigue and blood pressure-lowering effects of ginseng) and corpus cavernosum (thus, for the treatment of men suffering from erectile dysfunction; however, the legendary aphrodisiac effect of ginseng may be an overstatement). Many plant extracts or purified drugs derived from Chinese medicinal herbs with proposed actions on NO pathways are also reviewed.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"30 9","pages":"605-15"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1440-1681.2003.03885.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22548504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osmosensitive properties of rapid and slow delayed rectifier K+ currents in guinea-pig heart cells.","authors":"Toshitsugu Ogura,&nbsp;Hiroyuki Matsuda,&nbsp;Toshishige Shibamoto,&nbsp;Sunao Imanishi","doi":"10.1046/j.1440-1681.2003.03869.x","DOIUrl":"https://doi.org/10.1046/j.1440-1681.2003.03869.x","url":null,"abstract":"<p><p>1. Changes in cell volume affect a variety of sarcolemmal transport processes in the heart. To study whether osmotically induced cell volume shrinkage has functional consequences for K+ channel activity, guinea-pig cardiac preparations were superfused with hyperosmotic Tyrode's solution (1.2-2-fold normal osmolality). Membrane currents and cell surface dimensions were measured from whole-cell patch-clamped ventricular myocytes and membrane potentials were recorded from isolated ventricular muscles and non-patched myocytes. 2. Hyperosmotic treatment of myocytes quickly (< 3 min to steady state) shrank cell volume (approximately 20% reduction in 1.5-fold hyperosmotic solution) and depressed the delayed rectifier K+ current (IK). Analysis using different activation protocols and a selective inhibitor (5 micro mol/L E4031) indicated that the IK inhibition was due to osmolality and cell volume-dependent changes in the two subtypes of the classical cardiac IK (rapidly activating IKr and slowly activating IKs); 1.5-fold hyperosmotic treatment depressed the amplitudes of IKr and IKs by approximately 30 and 50%, respectively. 3. Superfusion of muscles and myocytes with 1.5-fold hyperosmotic solution lengthened the action potentials by 14-17%. Hyperosmotic treatment also caused 6-7 mV hyperpolarization that is most likely due to a concentrating of intracellular K+. 4. The inhibition of IK helps explain the lengthening of action potentials observed in osmotically stressed heart cells. These results, together with the reported IK stimulation by hyposmotic cell swelling, provide further support for cell volume-sensitive properties of cardiac electrical activity.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"30 9","pages":"616-22"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1440-1681.2003.03869.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22548505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac hypertrophy: a matter of translation.","authors":"R D Hannan,&nbsp;A Jenkins,&nbsp;A K Jenkins,&nbsp;Y Brandenburger","doi":"10.1046/j.1440-1681.2003.03873.x","DOIUrl":"https://doi.org/10.1046/j.1440-1681.2003.03873.x","url":null,"abstract":"<p><p>1. Left ventricular hypertrophy (LVH) of the heart is an adaptive response to sustained increases in blood pressure and hormone imbalances. Left ventricular hypertrophy is associated with programmed responses at the molecular and biochemical level in different subsets of cardiac cells, including the cardiac muscle cells (cardiomyocytes), fibroblasts, conductive tissue and coronary vasculature. 2. Regardless of the initiating cause, the actual increase in chamber enlargement is, in each case, due to an increase in size of a pre-existing cardiomyocyte population, with little or no change in their number; a process referred to as cellular hypertrophy. 3. An accelerated rate of global protein synthesis is the primary mechanism by which protein accumulation increases during cardiomyocyte hypertrophy. In turn, increased rates of synthesis are a result of increased translational rates of existing ribosomes (translational efficiency) and/or synthesis and recruitment of additional ribosomes (translational capacity). 4. The present review examines the relative importance of translational capacity and translational efficiency in the response of myocytes to acute and chronic demands for increased protein synthesis and the role of these mechanisms in the development of LVH.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"30 8","pages":"517-27"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1440-1681.2003.03873.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22507409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypocholesterolaemic effects of an ethanol precipitate of Kabosu juice in stroke-prone spontaneously hypertensive rats fed a cholesterol-free diet.","authors":"Hiroshi Ogawa,&nbsp;Satoshi Mochizuki","doi":"10.1046/j.1440-1681.2003.03870.x","DOIUrl":"https://doi.org/10.1046/j.1440-1681.2003.03870.x","url":null,"abstract":"<p><p>1. We have previously identified strong inhibitory effects of Kabosu (Citrus sphaerocarpa Hort.) juice precipitate (KJP) on cholesterol elevation in stroke-prone spontaneously hypertensive rats (SHRSP) fed a cholesterol diet. In the present study, to elucidate the hypocholesterolaemic mechanism, we examined the effect of dietary KJP on lipid metabolism by using SHRSP fed a cholesterol-free diet. 2. Compositions of the experimental diet containing 10% KJP powder were adjusted to those of the control diet. Seven-week-old male SHRSP were fed control or experimental diet for 2 weeks with free access to the diet and water. 3. Serum levels of cholesterol, phospholipid and triglyceride of the KJP group were significantly reduced, which was due to decreases in the very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions. 4. Serum concentrations of apolipoproteins A-I and E (apoA-I and E) of the KJP group were significantly lower than those of the control group, whereas no significant differences were observed in serum apoB and apoA-IV between the two groups. 5. In liver, there were no significant differences in the contents of lipids or relative liver weight between the two groups. The activity of microsomal cholesterol 7alpha-hydroxylase of the KJP group tended to increase, whereas that of microsomal acyl-coenzyme A : cholesterol acyltransferase was significantly reduced, compared with the control group. 6. These results indicate that dietary KJP produces reductions of serum lipid levels, which are due to reductions in VLDL, apoE HDL and apoA-I HDL, and may promote catabolism and excretion of hepatic cholesterol in SHRSP fed a cholesterol-free diet.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"30 8","pages":"532-6"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1440-1681.2003.03870.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22506808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical and morphological characterization of spontaneously hypertensive hyperlipidaemic rats.","authors":"Toshio Kumai,&nbsp;Shigeko Oonuma,&nbsp;Yasushi Kitaoka,&nbsp;Mamoru Tadokoro,&nbsp;Shinichi Kobayashi","doi":"10.1046/j.1440-1681.2003.03872.x","DOIUrl":"https://doi.org/10.1046/j.1440-1681.2003.03872.x","url":null,"abstract":"<p><p>1. To develop and characterize a new animal model of hypertension and hyperlipidaemia, we cross-bred spontaneously hypertensive rats (SHR) with spontaneously hyperlipidaemic rats (HLR). 2. A new strain of spontaneously hypertensive hyperlipidaemic rats (SHHR) was established at generation 10 through selective mating of brothers and sisters (systolic blood pressure > 150 mmHg, plasma cholesterol > 150 mg/dL). Cross-bred Wistar-Kyoto (WKY) rats and Sprague-Dawley (SD) rats (SDWKY rats) were used as a control. 3. Adrenaline and noradrenaline levels in the plasma and adrenal medulla of male SHHR were significantly higher than those of male SDWKY rats. The tyrosine hydroxylase activity in the adrenal medulla of male SHHR was significantly higher than that of male SDWKY rats. Low-density lipoprotein expression was found in the plasma of male and female SHHR and HLR. Cholesterol 7alpha-hydroxylase mRNA expression in the liver of male SHHR was lower than that of male SDWKY rats. Endothelium lesions and lipid deposition under the endothelium were observed in the aorta of 24-month-old SHHR, especially female SHHR, but not in age-matched HLR and SDWKY rats. 4. The hypertension of this new animal model of hypertension and hyperlipidaemia may be related to increased catecholamine activity and the hyperlipidaemia may be related to changes in the expression of cholesterol 7alpha-hydroxylase mRNA and lipoprotein profiles. The SHHR may be valuable in the study of mechanisms of atherosclerosis and the evaluation of anti-atherosclerosis drugs as a new strain of cardiovascular disease.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"30 8","pages":"537-44"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1440-1681.2003.03872.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22506809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of nitroglycerine in popliteal preparations from patients with peripheral occlusive arteriopathy precontracted with KCl or 5-hydroxytryptamine.","authors":"Ana Ortega,&nbsp;Martin Avellanal,&nbsp;Gabriel España,&nbsp;Angel Flores,&nbsp;Amaya Aleixandre","doi":"10.1046/j.1440-1681.2003.03875.x","DOIUrl":"https://doi.org/10.1046/j.1440-1681.2003.03875.x","url":null,"abstract":"<p><p>1. At the present time, there are no studies in isolated arteries from patients suffering from peripheral occlusive arteriopathy (POA). In the present study, we attempt to characterize the effect of nitroglycerine (GTN) in isolated popliteal preparations obtained after leg amputation in 60-90-year-old men and women suffering from POA. 2. After surgical operation, arterial samples were stored in a refrigerator at 4 degrees C and, after 12-36 h, they were cut into rings and mounted in organ baths containing Krebs'-Henseleit solution at 37 degrees C and gassed constantly with 95% CO2 and 5% O2. Because noradrenaline elicited very poor contractile responses in these preparations, in the present study we evaluated the concentration-dependent contractions induced by KCl (15-90 mmol/L) and 5-hydroxytryptamine (5-HT; 10-7 to 10-4 mol/L) in arteriopathic popliteal rings and, when the corresponding maximum contractile effect had been obtained, we also evaluated the concentration-dependent relaxing effect produced by GTN (10-10 to 10-5 mol/L) in all precontracted preparations. As a reference, similar experiments were performed in popliteal preparations obtained following surgery on non-arteriopathic vascular tissue where it was necessary to resect a certain percentage of healthy vessel. 3. The responses to KCl and 5-HT were greater in healthy vessel than in arteriopathic rings. The relaxing effect of GTN was greater in preparations precontracted with 5-HT than in those preparations precontracted with KCl. In addition, preparations precontracted with KCl relaxed even less when they were obtained from patients with POA. 4. The present data indicate that GTN is a vasodilator with little effect on depolarized arteries. The results also indicate that the effect of this drug is even less in depolarized arteries from patients with POA.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"30 8","pages":"528-31"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1440-1681.2003.03875.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22507410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purinoceptor-mediated contractility of the perfused uterine vasculature of the guinea-pig: influence of oestradiol and pregnancy.","authors":"John M Haynes,&nbsp;Jocelyn N Pennefather,&nbsp;Bogdan Sikorski","doi":"10.1046/j.1440-1681.2003.03839.x","DOIUrl":"https://doi.org/10.1046/j.1440-1681.2003.03839.x","url":null,"abstract":"<p><p>1. The effects of ATP, the stable ATP analogues alpha,beta-methylene ATP (alpha,beta-mATP), 2-methylthioATP (2meSATP) and adenosine tetraphosphate (ATP4), the pyrimidine nucleotide uridine 5'-triphosphate (UTP) and the alpha1-adrenoceptor agonist phenylephrine were examined on the isolated perfused uterine vasculature of dioestrous, oestradiol-treated, dexamethasone-treated and late-pregnant guinea-pigs. 2. The alpha1-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, alpha,beta-mATP was approximately two to three orders of magnitude more potent than 2meSATP. Compared with preparations from dioestrous animals, the maximal responses to alpha,beta-mATP were significantly greater in tissues from oestradiol-treated and pregnant animals. In preparations from dioestrous animals, the P2 purinoceptor antagonist suramin (100 micro mol/L) inhibited the responses to alpha,beta-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 alpha,beta-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.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"30 5-6","pages":"329-35"},"PeriodicalIF":0.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1440-1681.2003.03839.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22482442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of extracellular matrix and strain on proliferation of bovine airway smooth muscle.","authors":"John V Bonacci,&nbsp;Trudi Harris,&nbsp;Alastair G Stewart","doi":"10.1046/j.1440-1681.2003.03838.x","DOIUrl":"https://doi.org/10.1046/j.1440-1681.2003.03838.x","url":null,"abstract":"<p><p>1. The proliferation of airway smooth muscle (ASM) and collagen deposition are major contributors to airway remodelling in asthma that may be an important component of airway hyperresponsiveness. The ratio of collagen to laminin in asthma is increased as a result of fibrosis. 2. We investigated the effects of the extracellular matrix proteins laminin and collagen type I, as well as airway cell elongation (mechanical strain), on the proliferative responses of cultured bovine ASM cells and the impact of these biomechanical influences on glucocorticoid antimitogenic actions. 3. Bovine ASM cells were cultured onto a flexible silastic membrane coated with laminin or collagen. Cells were pretreated with dexamethasone (100 nmol/L) prior to incubation with the mitogen basic fibroblast growth factor (bFGF) for 72 h, at which time cells were enumerated. Cells were either subjected to mechanical strain (cell elongation) by stretching the flexible silastic membrane or were grown under static conditions. 4. Culture on collagen without elongation enhanced ASM proliferation compared with cells grown on laminin. Cells grown on laminin and subjected to 4% elongation did not respond to the mitogenic actions of bFGF. 5. Dexamethasone-mediated inhibition of bFGF-induced proliferation was unaffected by the extracellular matrix on which cells were seeded, or the degree of cell elongation. 6. These data support the hypothesis that the asthmatic airway wall microenvironment (collagen, reduced airway strain) enhances the proliferation of ASM cells.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"30 5-6","pages":"324-8"},"PeriodicalIF":0.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1440-1681.2003.03838.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22482444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}