ABSTRACT
Objectives: To explore the influence of exercise training on the arterial baroreflex sensitivity （BRS）and correlation between blood pressure and BRS in spontaneously hypertensive rats (SHR). Methods: Male SHR（n=20）and normotensive Wistar rats（n=20）were randomly assigned to normality group and exercise group, n=10 in each group. Rats in two exercise groups received treadmill training at a speed of 20 m/min for 60 min/d, 6 d/w for eight weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured using a tail-cuff method in a conscious state. Intravenous injections of phenylephrine (PE) and sodium nitroprusside (NP) were used to induce depressor and pressor reflex respectively. The ratio of HR over mean arterial pressure (MAP) (HR /MAP) after administration of PE or NP was regarded as an index of depressor reflex sensitivity (BRS-PE) and pressor reflex sensivity (BRS-NP). Results: After eight-week exercise training, compared with SHR normality group, there were significant reduction in resting SBP [(180±8.5) mmHg vs. (163.6±10.7) mmHg] and in HR [(368.4±13.3) beats/min vs. (345.0±9.8) beats/min] in SHR exercise group, P0.05), compared with Wistar normality group, there was significant reduction in HR [(362.2 ± 13.0) beats/min vs. (343.9 ± 10.2) beats/min, P <0.05] in Wistar exercise group. Compared with SHR normality group, there were significant rise in BRS [BRS-PE: (0.89 ± 0.13) bpm/mmHg vs. (1.32 ± 0.22) bpm/mmHg, BRS-NP： (0.60± 0.09) bpm/mmHg vs. (1.21± 0.26) bpm/mmHg, P<0.01] in SHR exercise group, but still lower than those of Wistar normality group [BRS-PE: (1.96±0.23) bpm/mmHg, BRS-NP: (1.32±0.17) bpm/mmHg]. Pearson linear correlation analysis indicated that MAP was significantly inversely correlated with BRS (r=-0.734, P<0.01) in SHR normality and exercise group. Conclusion: Exercise training may significantly decrease SHR blood pressure; it is related to improved baroreflex sensitivity induced by exercise, indicating that enhanced baroreflex may be an important mechanism of exercise therapy in hypertensive patients.
ABSTRACT
AIM: To investigate the effect of exercise training(EX) on the arterial baroreflex and possible mechanisms in rats with chronic heart failure(CHF).METHODS: Experiments were carried out in four groups: EX-CHF,CHF,EX-sham,and sham. CHF was induced by left coronary artery ligation,and EX consisted of 4 weeks of treadmill running. Baroreflex function,plasma angiotensin II(Ang II) and central AT1 receptor expression were determined.RESULTS: (1) The average slope and maximal gain of the baroreflex curve in CHF rats were lower than those in sham rats(P<0.01). EX significantly enhanced baroreflex parameters in CHF group but not in sham group.(2) EX decreased plasma Ang II in CHF rats ［(137±27)ng/L vs (263±55)ng/L,P<0.01］,but had no significant effect on plasma Ang II in sham rats ［(75±17)ng/L vs (92±21)ng/L］.(3) Expression of AT1R protein in the PVN of CHF rats was higher than that in sham rats(1.20±0.21 vs 0.70±0.14,P<0.01). EX reduced AT1R protein level in CHF rats(0.90±0.13),but had no impact in sham rats(0.60±0.16).CONCLUSION: EX restores the attenuated arterial baroreflex function in CHF rats,involving in decrease of plasma Ang II and downregulation of AT1R in the PVN.
ABSTRACT
The importance and necessity of undergraduates participating in the training plan of the medical research was clarified.Based on the actual ability of students and the characteristic of experimental teaching plan,we think that combination of experimental teaching of small group with research training is a strategy for enhancing the ability of the medical undergraduates to do research.This proposal will speed up the medical educational goal by the activation of novel idea,the cultivation of innovatory thought and the enhancement of creative ability.
ABSTRACT
Leukoencephalopathy with vanishing white matter(VWM) is one of the most prevalent inherited white matter disorders in childhood,and it′s the only known hereditary human disease due to the direct defects in protein synthesis process,with the gene defects in EIF2B1-5,encoding the five subunits of eukaryotic translation initiation factor(eIF2B ?,?,?,? and ?) respectively.eIF2B is essential for the protein translation initiation process,and its action is realized via eukaryotic translation initiation factor2(eIF2).Phosphorylation of eIF2? and eIF2B? is an important way to regulate eIF2B function,and thus play a key role in control of the protein translation level under physiological condition.Mutant eIF2B results in functional defects and decrease of the overall protein translation in cells,but in increase the translation of proteins with multiple upstream open reading frames,such as activating transcription factor 4(AFT4),which leads to the susceptibility to un-folded protein response under stress,and the following apoptosis.The exact pathogenic mechanisms of VWM are far from well understood.It′s suggested that level of AFT4 in cells with eIF2B mutations is higher than in wild type cells under physiological condition,which makes the mutant cells more susceptible to endoplasmic reticulum(ER) stress and unfolded protein response(UPR).Under stress,the defect eIF2B leads to a vicious cycle of UPR activation,which may underlie the neurological aggravation in VWM patients after minor stress,a specific cli-nical feature of VWM.Elucidating the pathogenesis of VWM will be helpful to further understand the protein translation process in eukaryotic cells,and provide a clue for possible therapeutic targets and treatment strategies in the future.Abstract:SUMM ARY Leukoencephalopathy with vanishing white matter(VWM) is one of the most prevalent in-herited white matter d isorders in childhood,and i′ts the only known hered itary human d isease due to the d irect defects in protein synthesis process,with the gene defects inEIF2B1-5,encod ing the five sub-units of eukaryotic translation initiation factor(eIF2B?,?,?,?and?) respectively.eIF2B is essential for the protein translation initiation process,and its action is realized via eukaryotic translation initiation factor2(eIF2).Phosphorylation of eIF2?and eIF2B?is an important way to regulate eIF2B function,and thus play a key role in control of the protein translation level under physiological cond ition.Mutant eIF2B results in functional defects and decrease of the overall protein translation in cells,but in increase the translation of proteins with multiple upstream open read ing frames,such as activating transcription factor 4(AFT4),which leads to the susceptibility to un-folded protein response under stress,and the following apoptosis.The exact pathogenic mechanisms ofVWM are far from well understood.I′ts sugges-ted that level ofAFT4 in cells with eIF2B mutations is higher than in wild type cells under physiological cond ition,which makes the mutant cellsmore susceptible to endoplasm ic reticulum(ER) stress and un-folded protein response(UPR).Under stress,the defect eIF2B leads to a vicious cycle ofUPR activa-tion,which may underlie the neurological aggravation in VWM patients afterm inor stress,a specific cli-nical feature ofVWM.E lucidating the pathogenesis ofVWM will be helpful to further understand the pro-tein translation process in eukaryotic cells,and provide a clue for possible therapeutic targets and treat-ment strategies in the future.
ABSTRACT
AIM:To determine the effect of reactive oxygen species on the baroreflex and to investigate the intracellular mechanism responsible for baroreflex dysfunction in the heart failure state.METHODS:In the rat model of cardiomyocytes infarct induced heart failure,baroreflex function was evaluated by measuring the relationship between renal sympathetic nerve activity(RSNA)responses and change of blood pressure by intravenous injection of nitroglycerin and phenylephrine.Alteration in baroreflex function was measured under the different reactive oxygen species(ROS)level induced by intracerebroventricular administration of several chemicals.RESULTS:(1)The range of RSNA response,average slope and maximum gain of baroreflex function curve were(92.2?9.9) mmHg,(0.07%?0.01%)/mmHg and(1.20%?0.10%)/mmHg,respectively,in CHF rats,which were significantly lower than those in sham rats(65.6?7.4) mmHg,(0.13%?0.02%)/mmHg and(3.00%? 0.20%)/mmHg(P