The present study investigated the role of calcineurin in angiotensin II(AngII)- induced cardiac myocyte hypertrophy of rats. Method. The primary cardiac myocytes were cultured under the standard conditions. The calci...The present study investigated the role of calcineurin in angiotensin II(AngII)- induced cardiac myocyte hypertrophy of rats. Method. The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII- treated cardiomyocytes was tested by using PNPP;protein synethsis rate was assessed by 3H- leucine incorporation; atrial natriuretic factor(ANF) mRNA level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase(LDH) levels in cultured medium and by dyed cell numbers. Result. After stimulation of 10,100 and 1 000nmol/L of AngII, calcineurin activities in the cardiomyocytes were increased by 13％ ,57％ (P Conclusion. During AngII- induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII- induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII- induced myocardial hypertrophy of rats.展开更多
The ACE （angiotensin converting enzyme） inhibitors are not only drugs widely prescribed drugs in cardiovascular diseases, but also potentially therapeutic agents in dementia. Based on the findings that the ACE inhib...The ACE （angiotensin converting enzyme） inhibitors are not only drugs widely prescribed drugs in cardiovascular diseases, but also potentially therapeutic agents in dementia. Based on the findings that the ACE inhibitors could activate the c-Jun N-terminal kinase signal to increase the ACE gene expression and that the Alu element of the human ACE gene involved in regulating ACE promoter activity, we aimed to investigate whether there are different pharmacogenetic responses of ACE I/D polymorphism to the ACE inhibitors in neurons. The three reporter vectors, pACEpro（0-SEAP, p-I-ACEpro-SEAP, and p-D-ACEpro-SEAP were used to examine the transcriptional activity of the vectors responding to the lisinopril treatment using a transient-transfection method in SH-SY5Y cells. Our results showed that lisinopril increased the promoter activity of an ACE gene by 16.7%. Additionally, we found the lisinopril enhanced the ACE promoter activity of the I-form vector by 17.2%, but adversely reduced that of the D-form vector by 16.8%, as compared with the respective control without the lisinopril treatment. Firstly, our findings had proved that the UD polymorphism of ACE gene contrarily responds to the ACE inhibitors in regulating the ACE expression in neurons, which provide a novel insight suggesting genetic testing to tailor the treatment regimens in AD （Alzheimer＇s disease） patients.展开更多
Hemorrhage or hypotension induces extensive Foslike immunoreactivity in the magnocellular neurosecretory cells in the supraoptic nucleus of the hypothalamus in rat, especially in the vasopressin neurons. The present s...Hemorrhage or hypotension induces extensive Foslike immunoreactivity in the magnocellular neurosecretory cells in the supraoptic nucleus of the hypothalamus in rat, especially in the vasopressin neurons. The present study was to explore the neurotransmitter mediating this effect. Microinfusion of the alpha-adrenergic blocker into the supraoptic nucleus reduced the hypotension-induced Fos, whereas beta-antagonist did not affect it significantly. Alpha1- and alpha2-antagonist, prazosin and yohimbine,both reduced the Fos-positive cell counts. However, the effective dosage of yohimbine was much larger. Alpha1-agonist, methoxamine, induced abundant Fos-like immnnoreactivity in the vasopressin cells in this nucleus,while beta-and alpha2-agonist did not elicit such effect.Administration of the noradrenergic re-uptake inhibitor,desipramine, to this nucleus to locally accumulate the spontaneously released noradrenaline from the nerve terminals also induced Fos expression, mostly in the vasopressin cells.展开更多
基金This work was supported by the research grants from National Natural Sciences Foundation of China(No. 39730220)
文摘The present study investigated the role of calcineurin in angiotensin II(AngII)- induced cardiac myocyte hypertrophy of rats. Method. The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII- treated cardiomyocytes was tested by using PNPP;protein synethsis rate was assessed by 3H- leucine incorporation; atrial natriuretic factor(ANF) mRNA level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase(LDH) levels in cultured medium and by dyed cell numbers. Result. After stimulation of 10,100 and 1 000nmol/L of AngII, calcineurin activities in the cardiomyocytes were increased by 13％ ,57％ (P Conclusion. During AngII- induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII- induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII- induced myocardial hypertrophy of rats.
文摘The ACE （angiotensin converting enzyme） inhibitors are not only drugs widely prescribed drugs in cardiovascular diseases, but also potentially therapeutic agents in dementia. Based on the findings that the ACE inhibitors could activate the c-Jun N-terminal kinase signal to increase the ACE gene expression and that the Alu element of the human ACE gene involved in regulating ACE promoter activity, we aimed to investigate whether there are different pharmacogenetic responses of ACE I/D polymorphism to the ACE inhibitors in neurons. The three reporter vectors, pACEpro（0-SEAP, p-I-ACEpro-SEAP, and p-D-ACEpro-SEAP were used to examine the transcriptional activity of the vectors responding to the lisinopril treatment using a transient-transfection method in SH-SY5Y cells. Our results showed that lisinopril increased the promoter activity of an ACE gene by 16.7%. Additionally, we found the lisinopril enhanced the ACE promoter activity of the I-form vector by 17.2%, but adversely reduced that of the D-form vector by 16.8%, as compared with the respective control without the lisinopril treatment. Firstly, our findings had proved that the UD polymorphism of ACE gene contrarily responds to the ACE inhibitors in regulating the ACE expression in neurons, which provide a novel insight suggesting genetic testing to tailor the treatment regimens in AD （Alzheimer＇s disease） patients.
文摘Hemorrhage or hypotension induces extensive Foslike immunoreactivity in the magnocellular neurosecretory cells in the supraoptic nucleus of the hypothalamus in rat, especially in the vasopressin neurons. The present study was to explore the neurotransmitter mediating this effect. Microinfusion of the alpha-adrenergic blocker into the supraoptic nucleus reduced the hypotension-induced Fos, whereas beta-antagonist did not affect it significantly. Alpha1- and alpha2-antagonist, prazosin and yohimbine,both reduced the Fos-positive cell counts. However, the effective dosage of yohimbine was much larger. Alpha1-agonist, methoxamine, induced abundant Fos-like immnnoreactivity in the vasopressin cells in this nucleus,while beta-and alpha2-agonist did not elicit such effect.Administration of the noradrenergic re-uptake inhibitor,desipramine, to this nucleus to locally accumulate the spontaneously released noradrenaline from the nerve terminals also induced Fos expression, mostly in the vasopressin cells.
