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自发性高血压大鼠组织多胺含量增加。

Enhanced tissue polyamine content in the spontaneously hypertensive rat.

作者信息

Ibrahim J, Hughes A D, Schachter M, Sever P S

机构信息

Department of Clinical Pharmacology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, United Kingdom.

出版信息

Clin Exp Pharmacol Physiol. 1996 May;23(5):410-4. doi: 10.1111/j.1440-1681.1996.tb02750.x.

Abstract
  1. Endogenous polyamines play a key role in mediating cellular growth and differentiation. Hypertension is associated with structural modifications of the circulatory system, a process that may be facilitated by polyamines. In this study, we examined whether there are elevated polyamine concentrations in the cardiovascular tissues of spontaneously hypertensive rats (SHR) relative to Wistar-Kyoto (WKY) rats. We also determined the chronic effect of 2% difluoromethylornithine (DFMO; a polyamine biosynthesis inhibitor) on tissue polyamines and hypertension. 2. SHR and WKY rats were treated with either 2% DFMO or drug-free drinking water; blood pressure was measured on alternate days and tissue polyamines were analysed at the end of the study. 3. We found that spermidine and spermine concentrations were markedly raised in the ventricles, resistance vessels and liver of the SHR, in comparison with corresponding tissues of WKY rats. DFMO did not affect SHR resistance vessel and liver polyamines, although spermidine in the ventricles was reduced. The blood pressure of neither SHR nor WKY rats was affected by DFMO. 4. In conclusion, this study shows for the first time a raised concentration of polyamines in the resistance vasculature of the SHR, in relation to their normotensive counterparts. The inability of DFMO to significantly reduce tissue polyamines in this study is in contrast to the effectiveness of 2% DFMO in other hypertension models, suggesting that polyamine homeostasis in this model may be stringently regulated.
摘要
  1. 内源性多胺在介导细胞生长和分化中起关键作用。高血压与循环系统的结构改变有关,多胺可能促进这一过程。在本研究中,我们检测了自发性高血压大鼠(SHR)心血管组织中的多胺浓度相对于Wistar-Kyoto(WKY)大鼠是否升高。我们还确定了2%二氟甲基鸟氨酸(DFMO;一种多胺生物合成抑制剂)对组织多胺和高血压的慢性影响。2. SHR和WKY大鼠分别用2% DFMO或无药饮用水处理;隔天测量血压,并在研究结束时分析组织多胺。3. 我们发现,与WKY大鼠的相应组织相比,SHR的心室、阻力血管和肝脏中的亚精胺和精胺浓度明显升高。DFMO对SHR阻力血管和肝脏多胺没有影响,尽管心室中的亚精胺减少了。DFMO对SHR和WKY大鼠的血压均无影响。4. 总之,本研究首次表明,相对于血压正常的对照大鼠,SHR阻力血管中的多胺浓度升高。在本研究中DFMO未能显著降低组织多胺,这与2% DFMO在其他高血压模型中的有效性形成对比,表明该模型中的多胺稳态可能受到严格调节。

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