As the first most common cause of death in China,stroke has become a public health problem that seriously affects national economy and people′s livelihood. Unfortunately,only 3% to 5% of stroke patients receive tissue plasminogen activator(tPA)treatment,the only pharmacological therapy ap?proved for ischemic stroke,and no drug is available for hemorrhagic stroke. Therefore,there is an ur?gent need to develop new drugs for stroke therapy. Despite the awareness that neuroprotective agents could be a common strategy for the treatment of both ischemic and hemorrhagic stroke,numerous neu?roprotective agents have showed failure in clinical trials. Combined with the current therapeutic strategies and drug development of stroke,this paper elaborated the stroke injury mechanisms and corresponding clinical drug research targeting excitotoxicity,oxidative and nitrosative stress,and inflammation. From a new perspective,this paper has proposed a novel therapeutic strategy targeting inherent defense mechanisms against stroke,with nicotinamide phosphoribosyltransferase(Nampt)- nicotinamide ade?nine dinucleotide defense system as an example to present our experimental evidence that Nampt can serve as an anti-stroke target and nicotinamide mononucleotide as an anti-stroke agent under development. It is hoped that the bottleneck of stroke therapy can be overcome with unremitting efforts so as to reduce the financial burden and mental stress,and bring benefits to people around the world.

The effects of sulmazole and isoprenaline on beating rate of cultured neonatal rat ventricular cardiomyocytes were measured with electrooptical technique. The results showed: (1) The spontaneous beating rate of primary cultured cardiomyocytes (culture for 72 h, 37?0.5℃, pH 7.2) was 134?16 beats/min (x?SD, n =41) and remained constant within 120 min. (2) The effect of sulmazole on beating rate was similar to that of isoprenaline. They both produced an apparent positive chronotropic action in a dose - dependent manner within a certain concentration range. The maximal responses between them were not statistical different.

The direct effect of Ketanserin (Ket) on heart rate and its mechanism were studied using isolated male Sprague-Dawley rat right atria. Ket (0.1-300?mol/L) produced apparent negative chronotropic action in a dose-dependent manner, the pD2 value was 4.8. Atropine (30 nmol/L) did not affect the negative chronotropic action of Ket Differing from the ?-receptor blocking agent propfanoloi (1?mol/L), Ket (1.5?mol/L) did not change the positive chronotropic dose-response curve for isoprenaline, but shifted the positive chronotropic dose-response curve for 5-hydroxytryptamine to the right and depressed its maximal response. These results indicate that the negative chronotropic action of Ket was related to the blockade of the 5-HT2-serotonergic receptor in the sinus node of rat atria, whereas the ?-adrenoreceptor and M-cholinergic receptor were not involved in the negative chronotropic action of Ket

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

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.

Objective:To establish a nicotine-treatment and-withdrawal rat model and to evaluate its characteristics and application through analyzing 3 parameters.Methods:Male Sprague-Dawley rats,aged 10-11 weeks old,were randomly divided into normal saline group(subcutaneous injection of saline [0.5 ml/kg] for 6 weeks),nicotine-treated group(injection with nicotine [0.5 ml/kg,3 mg/(kg?d)] for 6 weeks),and nicotine-withdrawn group(injection with nicotine [0.5 ml/kg,3 mg/(kg?d)] for 3 weeks and followed by saline injection for additional 3 weeks).Body weight,food intake,and water intake of animals were recorded during the treatment in 3 groups.The model was evaluated through analyzing body weight,serum parameters and adipose tissue weights.Results:The body weight of rats,as well as the serum levels of triglyceride and insulin,were all decreased after nicotine treatment;the weights of subcutaneous fat,visceral fat and periaortic fat were also decreased.The above indicators increased after withdrawal of nicotine.Conclusion:The established model can be used to study multiple pharmacological effects of nicotine;it can also be used for smoking and smoking cessation related studies.

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.

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.

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.

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.