Shibasaki M, Sudoh K, Asano M, Murakami K
Medicinal Research Laboratories II, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Eur J Pharmacol. 1992 May 14;215(2-3):271-6. doi: 10.1016/0014-2999(92)90038-6.
The effect of highly purified recombinant human renin (rh-renin), expressed in Chinese hamster ovary cells, on mean blood pressure (MBP) was evaluated in pithed spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Intravenous bolus injection of rh-renin produced dose-dependent increases in MBP in pithed SHR and WKY. The pressor response to rh-renin in pithed SHR was about 3 times as potent as that in pithed WKY. Intravenous infusion of rh-renin produced dose-dependent progressive increases in MBP during the first 40 min, reaching plateaus and thereafter MBP was maintained up to 120 min. This hypertensive response to rh-renin was antagonized by renin inhibitors, YM-21095 and KRI-1314, which inhibited the reaction between rh-renin and tetradecapeptide competitively, with Ki values of 5.1 x 10(-10) and 4.3 x 10(-9) M, respectively. In rh-renin-infused pithed SHR, the hypotensive effect of YM-21095 was 37 times as potent as that of KRI-1314. These results suggest that rh-renin can stimulate the rat renin-angiotensin system, thereby producing hypertension. Moreover, the rh-renin-infused rat model could be useful to evaluate the effect of renin inhibitor.
在去脑自发高血压大鼠（SHR）和Wistar-Kyoto大鼠（WKY）中评估了在中国仓鼠卵巢细胞中表达的高度纯化的重组人肾素（rh-肾素）对平均血压（MBP）的影响。静脉推注rh-肾素可使去脑SHR和WKY的MBP产生剂量依赖性升高。去脑SHR对rh-肾素的升压反应强度约为去脑WKY的3倍。静脉输注rh-肾素在最初40分钟内使MBP产生剂量依赖性逐渐升高，达到平台期，此后MBP维持长达120分钟。肾素抑制剂YM-21095和KRI-1314可拮抗这种对rh-肾素的高血压反应，它们竞争性抑制rh-肾素与十四肽之间的反应，Ki值分别为5.1×10^(-10)和4.3×10^(-9) M。在输注rh-肾素的去脑SHR中，YM-21095的降压作用强度是KRI-1314的37倍。这些结果表明，rh-肾素可刺激大鼠肾素-血管紧张素系统，从而产生高血压。此外，输注rh-肾素的大鼠模型可能有助于评估肾素抑制剂的作用。
