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Objective To determine the effects of trimetazidine (TMZ) on pathology and energy metabolism of myocardium in chronic renal failure(CRF) rats.Methods CRF models were built in Sprague-Dawley (SD) rats with 5/6 subtotal nephrectomy, and animals were randomyly divided into sham group, control group and three groups treated with different doses of TMZ (3 mg/kg,6 mg/kg or 9 mg/kg).TMZ was intragastrically administrated to CRF rats for 17 weeks, while physiologicalsalinewasusedascontrol. Transthoracicechocardiographywasperformedand myocardial morphosis was observed.Left ventricular weight/body weight(LVW/BW) and heart weight/body weight (HW/BW) were measured, and heart rate, and mean arterial pressure (MAP)were detected at the end of the study, while several parameters were detected, including urea nitrogen (BUN), creatinine(Scr), triphosaden(ATP), adenosine diphosphate(ADP), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α).Results (l)Left ventricle end-systolic dimensions, anterior wall end-diastolic and end-systolic thicknesses, and posterior wall end-diastolic thickness were significantly lower in rats treated with either medium dose or high dose of TMZ, as compared with control group(P＜0.05).(2)LVW/BW and HW/BW in rats treated with either medium dose or high dose of TMZ were significantly lower than those in control group(P＜0.05). (3)Various pathological changes were observed in control group, such as irregular arrangement and hypertrophy of the cardiomyocytes, myocardial fibrosis,mitochondrial swelling, focal muscle fiber dissolution, etc.However, all these pathological changes were apparently ameliorated in TMZ-treated groups, while the beneficial effects of TMZ therapy were dose-dependent. (4)No difference was observed in heart rate among all the groups.Although no difference existed in all the CRF rats, concerning on the systolic/diastolic blood pressure and mean arterial pressure (P＞0.05), these parameters were elevated in CRF rats, as compared with sham-operated group(P＜0.01). (5)ATP and ADP in TMZ-treated rats were significantly higher as compared with control(P＜0.05), moreover, medium dose and high dose of TMZ were superior to low dose (P＜0.05).(6)SOD was significantly increased in TMZ-treated rats (P＜0.05), while IL-6,TNF-α and MDA were significantly decreased in medium dose and high dose of TMZ, as compared with control(P＜0.05).Conclusion TMZ may prevent myocardial fibrosis and left ventricular hypertrophy in chronic renal failure via ameliorating myocardial energy metabolism and alleviating inflammatory reaction and oxidative stress.
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Objective:Clonidine,by activating peripheral α-sbrenoceptors, produces transient pressor response after i.v.injection in anesthetized animals.Moxonidine, with at least 40-fold higher affinity to I1-imidazoline receptors than to α2-adrenoceptors,produces also a transient pressor response. This work was designed to investigate whether I1-imidazoline receptors are involved in this pressor effect of moxonidine. Methods:Female spontaneously hypertensive rats(SHRs,aged 14-16 weeks)were anesthetized with urethane.To observe the transient pressor responses,moxonidine 0.1,0.3,1.0mg/kg(intravenous,i.v),2.0μg(intracerebroventricular,i.c.v.)and 1.0,10.0mg/kg(intragastric,i.g.)were administrated in different groups of rats.To evaluate the roles of α1-adrenoceptors,α2-adrenoceptors and I1-imidazoline receptors in the transient pressor responses to moxonidine, prazosin(10.0μg/kg),yohimbine(2.0mg/kg),phentolamine(0.2mg/kg),idazoxan(1.0mg/kg)or yohimbine+idazoxan(2.0mg/kg+1.0mg/kg)were intravenously given to the animals before moxonidine 0.3mg/kg (i.v.).Results:It was found that i.v.moxonidine produced a greater pressor response than clonidine when producing a similar reduction of blood pressure.This effect of moxonidine was not influenced by prazosin, but was partly inhibited by yohimbine, phentolamine or idazoxan,and completely blocked by the combination of yohimbine and idzaxon.Neither i.c.v.injection nor i.g. administration of moxonidine induced transient pressor responses.Conclusion:The transient pressor response of i.v. moxonidine is mediated by both peripheral I1-imidazoline receptors and α2-adrenoceptors.
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Objective:The present study was designed to test the hypothesis that inflammation is involved in the end-organ damage(EOD) induced by sinoaortic denervation(SAD) in rats.Method:SAD was performed in male Sprague-Dawley rats at the age of 10 weeks.Under anaesthesia,aortic nerves were cut and the sinus region of the carotid artery was stripped and painted with 10% phenol.Pathological evaluation of EOD and the determination of plasma or tissue levels of the factors related to inflammation,including thromboxane B2(TXB2) interleukin-1(IL-1),tumour necrosis factor α(TNF-α) and reactive oxygen species(ROS) were performed at 16 weeks after SAD.Pathological evaluation of EOD included heart weigh ratio,myocardial and blood vessel hydroxyproline and collagen volume fraction,glomerular injury score and number of infiltrating inflammatory cells.Indomethacin(20 mg/kg per day,orally) or vitamin E(100 mg/kg per day,orally) was administered for 12 weeks,beginning from4 weeks after SAD,to observe their effects on SAD-induced EOD.Results:There were significant fibrosis and inflammatory infiltration in the myocardium and blood vessels,represented by higher hydroxyproline and collagen volume fraction,and a large amount of inflammatory cells in the tissues of SAD rats.Heart weight and kidney glomerular injury score were significantly higher in ed significantly after SAD.Indomethacin and vitamin E significantly decreased the contents of some factors related to inflammation in SAD rats.Both drugs also alleviated myocardial and vessel fibrosis,inflammatory infiltration and kidney damage.Conclusion:Inflammation is involved in the organ damage induced by SAD in rats.
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Objective:It has been proposed that blood pressure variability(BPV) is positively related to end-organ damage(EOD) in hypertension.The present work was designed to observe the effects of long-term treatment with nitrendipine and hydralazine on BPV and EOD in spontaneously hypertensive rats(SHR),to examine the hypothesis that lowering BPV with an antihypertensive drug is an important factor in organ protection.Design and methods:Drugs were mixed in rat chow.After 4 months of drug administration,blood pressure was recorded continuously in conscious freely moving rats for 24 h.The heart,kidneys,and brain were then isolated and examined.Results:It was found that nitrendipine significantly decreased blood pressure and BPV,and significantly decreased EOD score in SHR.Hydralazine decreased blood pressure,but did not lower BPV.No effect on EOD was found in hydralazine-treated rats.In control rat(n=38),EOD score was weakly related to systolic blood pressure(r=0.331,P<0.05) and closely related to long-term systolic BPV(r=0.551,P<0.01).In nitrendipine-treated rats,EOD score was closely related to long-term systolic BPV(r=0.602,P<0.01),but not to blood pressure level(r=0.174,P>0.05).Conclusion:BPV plays an important role in the organ-protecting effects of nitrendipine.
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Objective:Glucose-insulin-potassium(GIK) is clinically used for reducing mortality in acute myocardial infarction(MI). It is known that ventricular arrhythmia, left ventricular dysfunction and impaired baroreflex sensitivity(BRS) are the three major determinants for predicting the mortality after acute MI. The present work was designed to study the effects of GIK on BRS, ventricular arrhythmia, and left ventricular function in rats with coronary artery ligature. Sprague-Dawley rats were used and the myocardial infarction was produced by ligature of the left anterior descending artery. Five weeks after coronary artery ligation, BRS was measured in conscious state with a computerized blood pressure monitoring system and left ventricular function and electrocardiogram were determined in the anaesthetized state in the subacute phase of myocardial infarction. It was found that GIK did not affect the blood pressure and heart period in both conscious and anaesthetized rats. GIK did not enhance BRS, but reduced ventricular arrhythmia and improved left ventricular function by reducing left ventricular end diastolic pressure in anaesthetized rats with MI. It is proposed that reducing ventricular arrhythmia and improving left ventricular function contribute to the effect of GIK on reducing the mortality after MI.
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It is well known that the arterial baroreflex(ABR)plays a key role in the regulation of heart rate and stabilization of blood pressure.Currently,it appears that ABR dysfunction is involved in the pathophysiology of cardiovascular disease states.Since the mid-1990s,a number of studies have been carried out in our laboratory to explore the pathological significance of ABR function in cardiovascular damage.This minireview summarizes our research work on the topic of ABR and left ventricular hypertrophy(LVH).On the basis of discussion concerning the importance of ABR dysfunction in hypertensive LVH and sinoaortic denervation-induced LVH,we advance a new strategy for reversal of LVH,that is,restoration of impaired ABR function.We tested this hypothesis in animal models with ABR deficiency.It was found that improvement of impaird ABR function with long-term treatment of ketanserin or candesartan was accompanied by reversal of LVH.The preliminary results indicate that it is feasible to target ABR for treatment of LVH.
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AIM To investigate the structural and functional remodeling of thoracic aortae in sinoaortic- denervated (SAD) rats. METHODS SD rats underwent either SAD or sham-operation at the age of 10 weeks. Sixteen weeks after operation, the contraction and relaxation of the thoracic aortae were measured in isolated preparations; The morphological changes of arteries were examined by using histopathological method and computer image analysis. RESULTS The NE-induced contraction was increased and Ach-induced relaxation of aortic rings was depressed in SAD rats; The structural remodeling of thoracic aortae was characterized by medial VSMC hypertrophy and matrix accumulations. CONCLUSION Vascular functional and structural remodeling can be found in sinoaortic-denervated rats.
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This article is based on the author's experience as the Associate Editor-in-Chief of 2 SCI-indexed journals and the invited reviewer for more than 10 international journals. Furthermore, the author has also published more than 75 original articles in SCI-indexed journals. This article summarizes the principles involved in preparing an original manuscript and choosing a suitable journal to submit. In addition, the detrimental effects of the increasing ethical misconducts (such as fabrication, falsification, plagiarism, duplicate submissions and publications) on the integrity of scientific publishing are pointed out and condemned.
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AIM: To investigate long-term effects of sinoaortic denervation (SAD) on the contraction and relaxation of thoracic aortae in rats.METHODS:SD rats underwent either SAD or sham operation at the age of 10 weeks. At 4,8, 16, and 32 weeks after operation, the contraction and relaxation of the thoracic aortae were measured by isolated artery technique.RESULTS:The NE-induced contraction and ACh-induced relaxation of aortic rings were progressively increased and depressed respectively after SAD.CONCLUSION:Vascular functional changes induced by purely blood pressure variability is similar to those observed in well-established experimental hypertensive states.
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Objective: To determine the effect of K ATP on the reduction of blood pressure variability (BPV) caused by adenosine in conscious, freely moving sinoaortic denervated (SAD) rats. Methods: Using computerized analytic system of blood pressure (BP), five groups treated with adenosine, adenosine A 1 receptor agonist N 6 cyclopentyladenosine (CPA), A 2 receptor agonist 5′ N cyclopropyl carboxamido adenosine (CPCA), ATP sensitive K + channel (K ATP ) blocker glibenclamide, and CPCA with the K ATP blocked by glibenclamide in advance were used. BP, heart period (HP) and BPV were analyzed. Results: Both adenosine and CPCA significantly decreased BPV in SAD rats, but CPA had no influence on it. Glibenclamide markedly reduced BPV in SAD rats as well, furthermore, it might antagonize the effect of CPCA on BPV by blocking K ATP . Conclusion: K ATP plays an important role in the development of high BPV in SAD rats. [
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Despite of great strides already made,China is still lagging behind Western countries in terms of scientific innovation,which is not parallel with China's economic achievement. Here I would like to summarize my experience in 30-year science research from the following two aspects:one is the motivation and source of innovation and the other is the value and implication of innovation. I will mainly focus on the relation of innovation with accidental discovery,reversed thought,long term accumulation,and challenge of the authorities. I will also discuss the great role of innovation in developing new theories,guiding medical practice,and dealing with emergencies.
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AIM: To study apoptosis and related genes expressions of cardiomyocytes in sinoaortic-denervated(SAD) rats. METHODS: SAD or sham-operation (Sham) was performed in male SD rats at the age of 10 weeks. After 16 weeks, apoptotic cells were stained in situ by terminal dexynucleotidyl-transferase mediated-dUTP nick end labeling (TUNEL). All stained results were analysised using computer image analysis techniques. Protein products and mRNA of Bcl-2, Bax, Fas and Fas-L were assessed by quantitative immunohistochemistry and RT-PCR. RESULTS: The numbers of apoptotic cardiomyocytes were significantly increased in SAD rats, the expressions of Bcl-2 were significantly decreased, whereas Bax,Fas and Fas-L were significantly increased in SAD rats. THZ]CONCLUSIONCONCLUSION: Apoptosis and dysregulation of gene expressions may be involved in the cardiomyocytes remodeling in SAD rats.
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Objective:The m ain objective was to exam ine the role of haemodynamics in rat aortic and left ventricular hy- pertrophy produced by sinoaortic denervation(SAD) .Methods:Rats were examined at different times after SAD or sham op- eration(Sham) .Haem odynamics were recorded continuously in conscious unrestrained rats.The time course of haemodynam ic changes and cardiovascular hypertrophy was observed and linear regression analysis was performed to study the role of haemodynam ics in SAD- induced aortic and left ventricular hypertrophy.L ong- term mortality,water and food intake,and body weight were also determ ined after operation.Results:High mortality(40 % ) ,dram atic reduction of water and food intake,and weight loss occurred within1week after SAD.Chronic SAD rats exhibited a marked increase in blood pressure variability (BPV) ,with no change in the average level of blood pressure(BP) ,as compared with the Sham control rats.Increased BPV was higher at2 weeks(about threefold) than16 weeks(about twofold) after SAD.Aortic hypertrophy existed in all3kinds of exam ined rats:2 - ,10 - and16 - week SAD rats.L eft ventricular hypertrophy was found only in10 - and16 - week SAD rats. Both aortic hypertrophy and left ventricular hypertrophy were significantly and positively correlated with BPV,but not with BP level.Conclusion:Persistent high BPV following SAD can lead to aortic and left ventricular hypertrophy.The aorta is more sensitive to increased BPV than the heart
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Objective:To investigate the protective effect of Intravenous Injection of Radix Astragali seu Hedysari on acute myocardiac infarction (AMI) in anesthetized dogs. Methods: Twenty health dogs were treated by ligating descending anterior of coronary with two-step method. The changes of electrocardiogram before and after ligation were recorded. After 4 hours myocardium were taken out and dyed with NBT to make sure of the extent of myocardiac infarction.Results: Intravenous Injection of Radix Astragali seu Hedysari could decrease the lethality of AMI, ameliorated ST changes on electrocardiogram induced by AMI, and reduced infarction area. Conclusions: Intravenous Injection of Radix Astragali seu Hedysari is effective in the treatment of AMI in anesthetized dogs.
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AIM To investigate the structural and functional remodeling of thoracic aortae in sinoaortic denervated (SAD) rats. METHODS SD rats underwent either SAD or sham operation at the age of 10 weeks. Sixteen weeks after operation, the contraction and relaxation of the thoracic aortae were measured in isolated preparations; The morphological changes of arteries were examined by using histopathological method and computer image analysis. RESULTS The NE induced contraction was increased and Ach induced relaxation of aortic rings was depressed in SAD rats; The structural remodeling of thoracic aortae was characterized by medial VSMC hypertrophy and matrix accumulations. CONCLUSION Vascular functional and structural remodeling can be found in sinoaortic denervated rats.
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AIM To investigate the changes of vascular systiolic/relaxant function in sino-aortic denervated rats. METHODS Male Sprague-Dawley rats were underwent sino-aortic denervation (SAD). The sinoaortic denervated (SAD) rats were adopted as a model of arterial baroreflex deficit. SAD, isolated aortic-denervated (AD) and isolated sinus-denervated (SD) rats were instrumented chronically to record blood pressure (BP), heart rate (HR), BP variability (BPV), HR variability (HRV), arterial baroreflex function control of heart period (ABR-HP) and BP (ABR-BP). The vascular maximum contractile/relaxant function was determined through cumulative venous injection of phenylephrine (SBP max ) and nitroprusside(DBP min ) both after ganglionic blokade. RESULTS Acute SAD(1 week after operation) caused hypertension and tachycardia in rats. Eighteen weeks after operation, BP and HR values in SAD and SD rats were not different from those in sham-operated rats, but AD rats were hypertensive compared with control group. Though the 24 h mean BP values of chronic (18 weeks after operation) SAD rats was not different from those in the sham-operated rats, 24 h BPV of SAD rats was significantly higher when compared with sham-operated rats. ABR function in the acute SAD rats was significantly decreased when compared with sham-operated rats, whereas in chronic SAD rats, both ABR-HP and ABR-BP were higher than those in acute SAD rats, but were still significantly lower than those in control groups. 18 weeks after operation, ABR function in SAD and AD rats were significantly decreased when compared with those in SD and control groups. SBP max after phenylephrine and DBP min after nitroprusside were significantly higher in SAD, AD and SD rats than in control group. ABR function was negatively correlated to DBP min ( r =-0.677 for ABR-HP, and r =-0.681 for ABR-BP; P
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Many studies, both retrospective and prospective, have shown that there is a circadian variation in acute cardiovascular events with a peak during the morning and a trough during the night since the mid 1980s. In addition to the morning peak, a secondary less prominent peak has been observed in the late afternoon in many studies. This circadian variation may well be at least partly linked to the known physiological circadian rhythms. Because the duration of the therapeutic effect of many drugs taken at the conventional time will have reached subtherapeutic levels at the time of waking and commencing activity the following morning, timing of medication is discussed to improve the protection of the patients with cardiovascular disease in the morning waking hours.
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The effects of tetrandrine and neferine on the phenylephrine-induced contractions were studied in Sprague-Dawley rat aortic rings. It was found that both tetrandrine and neferine ( 2?10-5 mol/L ) markedly inhibited phase I ( release of intracellular calcium) and phase II (entry of extracellular calcium) contractions after a 20 min incubation. After a shorter incubation period, tetrandrine and nefrine inhibited only the phase II contractions. Compared with tetrandrine, neferine exhibited slower and weaker effects
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40 weeks old SHR did not differ from that in slices of age matched WKY. B max was increased in the same brain region of SHR when compared to WKY. That rats of 4 5 weeks were in prehypertensive stage;rats of 10 12 weeks and above were at the stage of establishing hypertensive stage. Conclusion: The difference between SHR and normotensive rats in 5 HT 1A receptor binding in various brain regions may be related to the development of hypertension. When blood pressure changes,binding capacity of 5 HT 1A receptor in CNS changes accordingly.
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The contents of ir-arg-vasopressin (ir-AVP) and ir-?-endorphin (ir-?-EP) in plasma, anterior pituitary (AP), posterior pituitary (PP), oblongata (OB) and hypothalamus (HP) were measured by radioimmunoassay after sinoaortic denervation (SAD) in rats. It was showed that the ir-AVP contents in OB and ir-?-EP contents in AP, PP and OB were significantly elevated 1 d after (SAD) (P