共查询到20条相似文献,搜索用时 31 毫秒
1.
慢性缺氧大鼠心肌肌浆网功能及其钙泵基因表达的动态变化 总被引:1,自引:0,他引:1
将实验大鼠放置模拟5000m海拔高度低压舱内1、2和4周。结果表明:与对照组比较,1,2和4周组动物的心肌重量分别增加15%,18%和57%;心肌SRCa2+摄取分别降低33%,38%和53%;心肌SRCa2+ATPase活性分别降低54%,60%和74%;钙泵mRNA含量(基因表达分别降低14%,46%和68%。这些结果提示,缺氧导致的SR钙泵功能降低可能是心肌功能受损的重要生化基础之一,而钙泵数目减少可能是钙泵功能降低的分子生物学机制。 相似文献
2.
In vitro effects of hypoxia and (or) hypercapnic acidosis on the myocardial uptake of digoxin 总被引:1,自引:0,他引:1
A Sautegeau J P Clozel C Saunier D Hartemann 《Canadian journal of physiology and pharmacology》1985,63(4):344-346
A recent study has shown in the conscious dog that hypoxia associated with respiratory acidosis could increase the in vivo distribution of digoxin in the myocardium. The aim of the present study was to evaluate in vitro the effects of hypoxia and (or) hypercapnic acidosis on the digoxin uptake. For this purpose, rat myocardium was incubated for 180 min with radiolabelled [3H]digoxin. The uptake of digoxin which was expressed in nanograms of digoxin bound per 100 mg of myocardium was decreased by hypoxia and increased by hypercapnic acidosis. The association of hypoxia and hypercapnic acidosis had no effect on the digoxin uptake, suggesting that in vitro hypoxia acts in an opposite way to hypercapnia. 相似文献
3.
The authors investigated whether an altitude of 1,350 m would affect the rat cardiovascular system in the same way as genuine altitude hypoxia and the way it would take effect when combined with endurance training in the form of swimming It was found that 8 weeks spent at this altitude led to an increase in absolute and relative heart weight, to right ventricular hypertrophy, and to increased resistance of the myocardium to acute anoxia. Physical training at a moderate altitude resulted in an increase in the relative weight of the musculature of both the right and the left ventricle and of the septum. Unlike low altitude training, however, growth of the two compartments of the heart was proportional. The resistance of the myocardium of trained animals against anoxia was the same, irrespective of whether they trained at a low or a high altitude. The results show that even a moderate altitude is not a matter of indifference for the rat organism, but that it leads to characteristic manifestations of altitude hypoxia in the cardiovascular system. 相似文献
4.
5.
N K Khitrov A I Svistukhin E B Tezikov 《Biulleten' eksperimental'no? biologii i meditsiny》1979,87(6):523-525
Preliminary sympathectomia depletes acetylcholine (ACh) in the heart of rabbits under hypoxia. In these conditions the inhibitory action of ACh on the rat isolated heart is reduced under the noradrenaline content fall, while under increase it is potentiated. Under hypoxia noradrenaline increases concentration of potassium in the myocardium, thus stimulating ACh formation and activity. It is suggested that under deep hypoxia suppression of the sympathetic mechanisms causes functional isolation of the heart from nervous effects. 相似文献
6.
Tong W Xue Q Li Y Zhang L 《American journal of physiology. Heart and circulatory physiology》2011,301(5):H2113-H2121
Fetal hypoxia leads to progressive cardiac remodeling in rat offspring. The present study tested the hypothesis that maternal hypoxia results in reprogramming of matrix metalloproteinase (MMP) expression patterns and fibrillar collagen matrix in the developing heart. Pregnant rats were treated with normoxia or hypoxia (10.5% O(2)) from day 15 to 21 of gestation. Hearts were isolated from 21-day fetuses (E21) and postnatal day 7 pups (PD7). Maternal hypoxia caused a decrease in the body weight of both E21 and PD7. The heart-to-body weight ratio was increased in E21 but not in PD7. Left ventricular myocardium wall thickness and cardiomyocyte proliferation were significantly decreased in both fetal and neonatal hearts. Hypoxia had no effect on fibrillar collagen content in the fetal heart, but significantly increased the collagen content in the neonatal heart. Western blotting revealed that maternal hypoxia significantly increased collagen I, but not collagen III, levels in the neonatal heart. Maternal hypoxia decreased MMP-1 but increased MMP-13 and membrane type (MT)1-MMP in the fetal heart. In the neonatal heart, MMP-1 and MMP-13 were significantly increased. Active MMP-2 and MMP-9 levels and activities were not altered in either fetal or neonatal hearts. Hypoxia significantly increased tissue inhibitors of metalloproteinase (TIMP)-3 and TIMP-4 in both fetal and neonatal hearts. In contrast, TIMP-1 and TIMP-2 were not affected. The results demonstrate that in utero hypoxia reprograms the expression patterns of MMPs and TIMPs and causes cardiac tissue remodeling with the increased collagen deposition in the developing heart. 相似文献
7.
A A Korneev O A Popova S V Zamula L D Luk'ianova 《Biulleten' eksperimental'no? biologii i meditsiny》1990,110(7):60-63
The effect of hypoxia of middle severity (H50) has been investigated on the contractile activity, oxidative metabolism and bioenergetic function of the myocardium in the isolated rat heart. It has been shown that differences in the functional-metabolic parameters sensitivity in the resistant and non-resistant to hypoxia animals are defined by the primary utilization of different pathways of substrates oxidation--the succinate-oxidative pathway of oxidation or the NADH-oxidative pathway, correspondingly. It is possible to correct the early hypoxic injuries of the electron-transfer function of the myocardium respiratory chain at the NADH-CoQ region (the first enzyme complex) with the help of quinones (vitamin K3, hydroquinone). The mechanism of this correction depends on the donor-acceptor properties of these compounds and it is the same both in the myocardium of the isolated heart and in the isolated mitochondria. Vitamin K3 is recommended to be utilized on the early stages of hypoxic injuries in myocardium as an antihypoxant of the energized type. 相似文献
8.
D Jarkovská B Ostádal 《Virchows Archiv. B, Cell pathology including molecular pathology》1983,43(3):327-336
Seven-day-old mice, strain H, were exposed to intermittent high altitude hypoxia (IHA) in a barochamber (7,000 m, 4 h/day, 5 days a week); a total number of exposures was 10. It has been shown that the layer of cardiac musculature in the adventitia of the pulmonary veins, the so-called pulmonary myocardium, reacts to IHA hypoxia by enlargement even sooner than the right ventricular myocardium. The average thickness of the layer of pulmonary myocardium was significantly greater in animals exposed to IHA hypoxia as compared with the controls. Furthermore, IHA hypoxia induces the extension of the pulmonary myocardium to the periphery of the pulmonary venous bed. Ultrastructural investigation of the pulmonary myocardium in hypoxic animals revealed the presence of unoriented myofilaments in the peripheral myofibril-free sarcoplasma, increase in the number of ribosomes and appearance of profiles of granular endoplasmic reticulum. Our data provide quantitative support for the hypothesis that it is not only the contraction of pulmonary arteries, but also venoconstriction which contribute to the hypoxic pressure response in mice. 相似文献
9.
丹参对心肌低氧/复氧损伤的保护作用的研究 总被引:7,自引:0,他引:7
目的:研究中药丹参(SM)对心肌低氧/复氧损伤的保护作用。方法:运用^31P-NMR技术对离体灌流大鼠心脏的高能磷酸化合物含量及细胞内的pH值(pHi)进行动态跟踪。结果:丹参注射液能明显减轻低氧期间心肌高能磷酸合物含量的下降,促使复氧期间PCr、ATP相对含量的恢复,减少低氧及复氧阶段心肌pHi的下降。结论:丹参参改善低氧及复氧期间心肌能量代谢水平,减轻心肌低氧/复氧损伤,并能显著改善细胞内酸碱 相似文献
10.
M Wachtlová V Mares B Ostádal 《Virchows Archiv. B, Cell pathology including molecular pathology》1977,24(4):335-342
Intermittent high altitude (IHA) hypoxia (7000 m) increased the wet weight of the right ventricular myocardium of 30-day-old rats after two 4 h/day exposures. During the same period the number of DNA-synthesizing nuclei of both muscle and non-muscle cell types increased proportionally. After 4 such exposures to hypoxia the number of 3H-thymidine-labelled nuclei in both cell types increased further. In addition, the number of labelled nuclei increased significantly in the yet un-enlarged left ventricle. While there was no difference in the number of DNA-synthesizing cells between the right and left ventricles in control animals, a significant increase in the number of cells involved in DNA synthesis in the right ventricle was found in both groups of animals exposed to IHA hypoxia. These results show that DNA synthesis in myonuclei of the ventricular myocardium can be stimulated in 30-day-old rats, i.e. at the very end of the weaning period. 相似文献
11.
Vairetti M Carini R De Cesaris MG Splendore R Richelmi P Bertè F Albano E 《Biochimica et biophysica acta》2002,1587(1):83-91
Liver hypoxia still represents an important cause of liver injury during shock and liver transplantation. We have investigated the protective effects of beta-alanine against hypoxic injury using isolated perfused rat livers and isolated rat hepatocyte suspensions. Perfusion with hypoxic Krebs-Henseleit buffer increased liver weight and caused a progressive release of lactate dehydrogenase (LDH) in the effluent perfusate. The addition of 5 mmol/l beta-alanine to the perfusion buffer completely prevented both weight increase and LDH leakage. These findings were confirmed by histological examinations showing that beta-alanine blocked the staining by trypan blue of either liver parenchymal and sinusoidal cells. Studies performed in isolated hepatocytes revealed that beta-alanine exerted its protective effects by interfering with Na+ accumulation induced by hypoxia. The addition of gamma-amino-butyric acid, which interfered with beta-alanine uptake by the hepatocytes or of Na+/H+ ionophore monensin, reverted beta-alanine protection in either hepatocyte suspensions or isolated perfused livers. We also observed that liver receiving beta-alanine were also protected against LDH leakage and weight increase caused by the perfusion with an hyposmotic (205 mosm) hypoxic buffer obtained by decreasing NaCl content from 118 to 60 mmol/l. This latter effect was not reverted by blocking K+ efflux from hepatocyte with BaCl(2) (1mmol/l). Altogether these results indicated that beta-alanine protected against hypoxic liver injury by preventing Na+ overload and by increasing liver resistance to osmotic stress consequent to the impairment of ion homeostasis during hypoxia. 相似文献
12.
低氧预处理对低氧/复氧心肌能量代谢的作用 总被引:4,自引:0,他引:4
目的:研究低氧预处理(HPC)对心肌的保护作用,方法:借助^31P-NMR图谱技术,在模拟Langendorff离体灌流大鼠心脏的正常生理条件下,跟踪心肌高能磷酸化合物含量的动态变化。结果:在30min低氧期,PCr、ATP相对含量及PCr/Pi值逐渐减小,但HPC组减小的速度比对照组慢;而在复氧期,HPC组能提高心肌高能磷酸化合物含量的恢复程度,特别是复氧初期,HPC组PCr 、ATP相对含量及PCr/Pi值立即有了恢复;在本实验中,HPC对pHi的改善不显著。结论:HPC能降低后续长时间低氧及复氧阶段的心肌能量代谢,对心肌的低氧/复氧损伤具有保护作用。 相似文献
13.
L Gordon J Wharton S E Moore T P Flanigan S Gulbenkian F S Walsh J F David-Ferreira R J Winter J M Polak 《Life sciences》1990,47(7):601-609
Myocardial neural cell adhesion molecule (N-CAM) is temporally regulated, being expressed during cardiac morphogenesis and innervation and suppressed in the adult heart. We have investigated the plasticity of N-CAM expression in hypertrophic muscle using the rat model of chronic hypoxia to selectively induce right ventricular hypertrophy over a 14 day time course. Sarcolemmal and intercalated disc N-CAM immunostaining was more extensive in the ventricular myocardium of hypoxic rats compared to normoxic controls. Quantitative assessment of the immunoreactivity in tissue extracts demonstrated a selective increase in the amount of N-CAM immunoreactivity in the hypertrophic myocardium of the right ventricle of rats exposed to hypoxia and this was associated with an increase of the 125 kDa isoform. We conclude that myocardial hypertrophy may be a factor influencing N-CAM expression in the heart and adhesion molecules may have a role in cardiac remodelling. 相似文献
14.
A A Podkolzin S O Trenin A P Legoshin A V Khokhlov 《Biulleten' eksperimental'no? biologii i meditsiny》1991,112(8):128-130
It has been established in 23 experiments on dogs that during asphyxia the reactions of denervated heart which were directed toward compensation of hypoxia in the whole organism and towards preservation of myocardium from hypoxia damages were slower than that in the norm. All these processes led to the overloading of myocardium. 相似文献
15.
Effects of adaptation to periodic hypoxia on bioelectric activity of cardiomyocytes of isolated heart in ischemia and reperfusion 总被引:1,自引:0,他引:1
Experiments on isolated Wistar rat heart perfused according to Langendorff showed that preliminary adaptation of rats to intermittent hypobaric hypoxia limited the fall of values of the resting potential and the amplitude and duration of action potential characteristic for ischemia. Under similar conditions, adaptation considerably reduced the increased time of impulse conduction along the myocardium. In reperfusion, the parameters enumerated restored much more efficiently in hearts from adapted animals than in controls. The role of these changes in the antiarrhythmic effect of adaptation to intermittent hypoxia is under discussion. 相似文献
16.
Inka Liesmaa Hanna K. Leskinen Jorma O. Kokkonen Heikki Ruskoaho Petri T. Kovanen Ken A. Lindstedt 《Journal of cellular physiology》2009,221(2):359-366
Bradykinin receptors are differentially expressed in the coronary vascular endothelium of rat and human hearts during the pathogenesis of heart failure, but the mechanisms responsible for this regulation have remained vague. Here we show by quantitative real-time PCR, Western blot analysis, and immunohistochemistry, that hypoxia triggers the expression of bradykinin type-2 receptors (BK-2Rs) in cultured human coronary artery endothelial cells (HCAECs), in isolated rat cardiac microvascular endothelial cells (RCMECs), and in rat hearts subjected to ligation of the left anterior descending coronary artery. Mild hypoxia (5% O2) induced a fourfold temporal increase in BK-2R mRNA expression in HCAECs, which was also observed at the protein level, whereas severe hypoxia (1% O2) slightly inhibited the mRNA expression of BK-2Rs. In addition, HOE-140, a BK-2R antagonist, inhibited mRNA and protein expression of BK-2Rs. The BK-2Rs induced by mild hypoxia were biologically active, that is, capable of inducing intracellular production of nitric oxide (NO) upon activation of HCAECs with bradykinin (BK), a response attenuated by HOE-140. In rat hearts recovering from myocardial infarction, BK-2Rs were upregulated in the endothelium of vessels forming at the border zone between fibrotic scar tissue and healthy myocardium. Furthermore, in an in vitro wound-healing assay, RCMEC migration was increased under mild hypoxic culture conditions in the presence of BK and was attenuated with HOE-140. Our present results show that mild hypoxia triggers a temporal expression of functional BK-2Rs in human and rat endothelial cells and support a role for BK-2Rs in hypoxia-induced angiogenesis. J. Cell. Physiol. 221: 359–366, 2009. © 2009 Wiley-Liss, Inc. 相似文献
17.
Caretti A Morel S Milano G Fantacci M Bianciardi P Ronchi R Vassalli G von Segesser LK Samaja M 《Experimental biology and medicine (Maywood, N.J.)》2007,232(7):887-894
To study the in vivo dynamics of hypoxia-inducible factor 1alpha (HIF-1alpha), master regulator of O(2)-dependent gene expression, and mitogen-activated protein kinases (MAPKs) in the hypoxic myocardium, Sprague-Dawley rats (n = 4 to 6 per group) were exposed to 1-hr hypoxia (10% O(2)), 23-hr hypoxia, and 23-hr hypoxia, followed by reoxygenation. HIF-1alpha increased 15-fold after 1-hr hypoxia, remained constant for 23 hrs, and returned to baseline on reoxygenation. Extracellular signal-regulated kinases (ERK1/2) were unchanged throughout. Phosphorylated p38 increased 4-fold after 1-hr hypoxia and returned to baseline within 23-hr hypoxia. The activity of stress-activated protein kinases/c-Jun NH(2)-terminal kinases (JNKs), measured as phosphorylated c-Jun, increased 3-fold after 1-hr hypoxia and remained sustained afterward. Furthermore, HIF-1alpha was halved in rats that were administered with the p38 inhibitor SB202190 and made hypoxic for 1 hr. In conclusion, although very sensitive to the reoxygenation, HIF-1alpha is overexpressed in vivo in the hypoxic myocardium, and its acute induction by hypoxia is correlated with that of p38. 相似文献
18.
Protein remodeling of extracellular matrix in rat myocardium during four-day hypoxia: the effect of concurrent hypercapnia 总被引:1,自引:0,他引:1
The combination of long-term hypercapnia and hypoxia decreases pulmonary vascular remodeling and attenuation of right ventricular (RV) hypertrophy. However, there is limited information in the literature regarding the first stages of acclimatization to hypercapnia/hypoxia. The purpose of this study was to investigate the effect of four-day hypoxia (10% O2) and hypoxia/hypercapnia (10% O2 + 4.4% CO2) on the protein composition of rat myocardium. Expression of the cardiac collagen types and activities of matrix metalloproteinases (MMPs) and of their tissue inhibitor TIMP-1 were followed. The four-day hypoxia changed protein composition of the right ventricle only in the hypercapnic condition; remodeling was observed in the extracellular matrix (ECM) compartments. While the concentrations of pepsin-soluble collagenous proteins in the RV were elevated, the concentrations of pepsin-insoluble proteins were decreased. Furthermore, the four-day hypoxia/hypercapnia increased the synthesis of cardiac collagen due to newly synthesized forms; the amount of cross-linked particles was not affected. This type of hypoxia increased cardiac collagen type III mRNA, while cardiac collagen type I mRNA was decreased. MMP-2 activity was detected on the zymographic gel through appearance of two bands; no differences were observed in either group. mRNA levels for MMP-2 in the RV were significantly lower in both the hypoxic and hypoxic/hypercapnic animals. mRNA levels for TIMP-1 were reduced in the RV of both the hypoxic and hypoxic/hypercapnic animals. Hypoxia with hypercapnia increased the level of mRNA (6.5 times) for the atrial natriuretic peptide (ANP) predominantly in the RV. The role of this peptide in remodeling of cardiac ECM is discussed. 相似文献
19.
Allopurinol Enhances Adenine Nucleotide Levels and Improves Myocardial Function in Isolated Hypoxic Rat Heart 总被引:1,自引:0,他引:1
Allopurinol, a competitive inhibitor of xanthine oxidase, was found to have a protective effect on ischemic myocardium. Its mechanism of action is still controversial. We used Langendorff isolated rat heart preparation to test the hypothesis that allopurinol could maintain a level of the adenine nucleotide pool (ATP, ADP, and AMP) that would protect and improve the functional activity of the heart during a period of hypoxia. Hearts were initially perfused for 30 min until steady state was attained. This was followed by 20 min of experimental perfusion divided into 5 min of control perfusion followed by 15 min of hypoxic perfusion with or without allopurinol in the perfusate. Hearts were quick-frozen and enzymatically analyzed for adenine nucleotides and creatine phosphate at the end of the hypoxic period. Left ventricular pressure, heart rate, and coronary flow were measured in all preparations. Allopurinol (0.1 mM) treated hearts had greater levels of ATP (12.3 ± 0.8 vs. 9.3 ± 0.8 µmol/g dry weight; p < 0.01). This improvement occurred in the presence as well as the absence of glucose. Total adenine nucleotides improved from 17 ± 1 to 20.3 ± 2.4 µmol/g dry weight (p < 0.01). This improvement also occurred in the presence as well as in the absence of glucose in the perfusate. It also improved cell energy state significantly in the presence as well as the absence of glucose. There was insignificant change in creatine phosphate. Allopurinol improved left ventricular pressure from 38 ± 7% to 55 ± 9% (p < 0.002) in the presence of glucose and from 8 ± 3% to 27 ± 6.3% (p < 0.001) in the absence of glucose. Coronary flow improved from 110 ± 5% to 120 ± 8% (p < 0.04) in the presence of glucose. These results support the suggestion that allopurinol at 0.1 mM exerts its protective effect on rat heart during hypoxia by enhancing the adenine nucleotide pool. 相似文献
20.
Nitric oxide (NO) is an important vascular modulator in the development of pulmonary hypertension. NO exerts its regulatory effect mainly by activating soluble guanylate cyclase (sGC) to synthesize cyclic guanosine monophosphate (cGMP). Exposure to hypoxia causes pulmonary hypertension. But in lung disease, hypoxia is commonly accompanied by hypercapnia. The aim of this study was to examine the changes of sGC enzyme activity and cGMP content in lung tissue, as well as the expression of inducible nitric oxide synthase (iNOS) and sGC in rat pulmonary artery after exposure to hypoxia and hypercapnia, and assess the role of iNOS-sGC-cGMP signal pathway in the development of hypoxic and hypercapnic pulmonary hypertension. Male Sprague-Dawley rats were exposed to hypoxia and hypercapnia for 4 weeks to establish model of chronic pulmonary hypertension. Weight-matched rats exposed to normoxia served as control. After exposure to hypoxia and hypercapnia, mean pulmonary artery pressure, the ratio of right ventricle/left ventricle+septum, and the ratio of right ventricle/body weight were significantly increased. iNOS mRNA and protein levels were significantly increased, but sGC α(1) mRNA and protein levels were significantly decreased in small pulmonary arteries of hypoxic and hypercapnic exposed rat. In addition, basal and stimulated sGC enzyme activity and cGMP content in lung tissue were significantly lower after exposure to hypoxia and hypercapnia. These results demonstrate that hypoxia and hypercapnia lead to the upregulation of iNOS expression, downregulation of sGC expression and activity, which then contribute to the development of pulmonary hypertension. 相似文献