Hamet P, Malo D, Hashimoto T, Tremblay J
Clinical Research Institute of Montreal, Quebec, Canada.
J Hypertens Suppl. 1990 Dec;8(7):S47-52.
Genetically hypertensive animals such as spontaneously hypertensive rats (SHR) and mice are more sensitive to thermal stress than normotensive controls. Genetic breeding experiments have demonstrated that the gene responsible for thermosensitivity segregates with an increase in blood pressure in the F2 generation and represents a genetic locus of hypertension. Due to a higher transcription rate of the heat shock protein 70 (hsp70) gene, which is a major heat stress gene, the accumulation of hsp messenger (m)RNA is increased in hypertension. Higher thermosensitivity and increased hsp mRNA accumulation are also observed in neonatal cardiomyocytes and cultured vascular smooth muscle cells from SHR, suggesting that these abnormalities are primary in character. This higher hsp70 transcription rate in hypertension could be due to an abnormality in the promoter region, to an interaction between heat stress trans-acting factor and heat stress element within the promoter of hsp70 or to an abnormal activation of heat stress trans-acting factor. A study using recombinant inbred animals has indicated that RT1 complex gene(s), a major histocompatibility complex in the rat, may be involved in the development of hypertension. These findings, together with the fact that hsp70 is located in the major histocompatibility complex, suggest that hsp70 gene or associated genes within the RT1 complex are responsible for environmental control of the expression of hypertension.
遗传性高血压动物，如自发性高血压大鼠（SHR）和小鼠，比血压正常的对照动物对热应激更敏感。遗传育种实验表明，负责热敏感性的基因在F2代中随着血压升高而分离，代表了一个高血压基因位点。由于主要热应激基因热休克蛋白70（hsp70）基因的转录率较高，hsp信使核糖核酸（mRNA）在高血压中的积累增加。在SHR的新生心肌细胞和培养的血管平滑肌细胞中也观察到较高的热敏感性和hsp mRNA积累增加，这表明这些异常具有原发性。高血压中较高的hsp70转录率可能是由于启动子区域异常、热应激反式作用因子与hsp70启动子内的热应激元件之间的相互作用，或热应激反式作用因子的异常激活。一项使用重组近交系动物的研究表明，大鼠主要组织相容性复合体RT1复合体基因可能参与高血压的发生发展。这些发现，连同hsp70位于主要组织相容性复合体内这一事实，表明hsp70基因或RT1复合体内的相关基因负责高血压表达的环境调控。
