Kubo T, Ikezawa A, Kambe T, Hagiwara Y, Fukumori R
Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo, Japan.
Brain Res Bull. 2001 Sep 1;56(1):23-8. doi: 10.1016/s0361-9230(01)00586-x.
Brain renin-angiotensin system plays an important role in blood pressure regulation and is suggested to play a role in the development and maintenance of hypertension. To test the hypothesis that brain renin may play a significant role in hypertension in spontaneously hypertensive rats (SHR), phosphorothioated antisense oligodeoxynucleotides targeted to renin mRNA were administered intracerebroventricularly in SHR. Administration of an antisense but not its sense oligodeoxynucleotide produced a prolonged duration of decrease in blood pressure. Intra-arterial administration of the antisense oligodeoxynucleotide at the same dose that decreased blood pressure when administered intraventricularly did not affect blood pressure. Furthermore, renin mRNA but not angiotensin AT1 receptor mRNA levels were decreased in the hypothalamus of the antisense oligodeoxynucleotide-treated rats. These results suggest that brain renin may play a significant role in hypertension in SHR.
脑肾素-血管紧张素系统在血压调节中起重要作用，并且提示其在高血压的发生和维持中发挥作用。为了验证脑肾素可能在自发性高血压大鼠（SHR）的高血压中起重要作用这一假说，将靶向肾素mRNA的硫代磷酸化反义寡脱氧核苷酸经脑室注射给予SHR。给予反义寡脱氧核苷酸而非其正义寡脱氧核苷酸可使血压下降的持续时间延长。以脑室注射时能降低血压的相同剂量经动脉给予反义寡脱氧核苷酸并不影响血压。此外，反义寡脱氧核苷酸处理的大鼠下丘脑肾素mRNA水平降低，但血管紧张素AT1受体mRNA水平未降低。这些结果提示脑肾素可能在SHR的高血压中起重要作用。
