Kitami Y
Second Department of Internal Medicine, Ehime University, School of Medicine, Japan.
Nihon Jinzo Gakkai Shi. 1990 Apr;32(4):427-33.
Effect of renin inhibitor ES-1005 or captopril on the renin synthesis by the kidney was investigated in sodium-depleted marmosets. The level of kidney renin mRNA was measured after 2-hour (acute study) and one-week (chronic study) administrations of the two agents. Relative amounts of kidney renin mRNA were measured by densitometric Northern blot analysis using an alpha-32P-labelled human renin cDNA fragment as a hybridization probe. In the acute study, treatment with captopril significantly increased plasma renin activity (PRA) (p less than 0.05), but did not change the level of kidney renin mRNA. In the chronic study, treatment with captopril markedly increased PRA as well as the level of kidney renin mRNA (4.7-fold and 6.3-fold increases, respectively). In contrast, treatment with ES-1005 completely inhibited PRA and significantly suppressed the level of kidney renin mRNA in both acute and chronic studies (about one-third of the normal control, p less than 0.05). These results suggest that renin inhibitor ES-1005 not only inhibits plasma renin activity but also suppresses the synthesis of renin by the kidney.
在钠缺乏的狨猴中研究了肾素抑制剂ES - 1005或卡托普利对肾脏肾素合成的影响。在给予这两种药物2小时(急性研究)和1周(慢性研究)后,测量肾脏肾素mRNA水平。使用α - 32P标记的人肾素cDNA片段作为杂交探针,通过光密度Northern印迹分析测量肾脏肾素mRNA的相对含量。在急性研究中,卡托普利治疗显著增加了血浆肾素活性(PRA)(p < 0.05),但未改变肾脏肾素mRNA水平。在慢性研究中,卡托普利治疗显著增加了PRA以及肾脏肾素mRNA水平(分别增加4.7倍和6.3倍)。相比之下,在急性和慢性研究中,ES - 1005治疗均完全抑制了PRA,并显著抑制了肾脏肾素mRNA水平(约为正常对照的三分之一,p < 0.05)。这些结果表明,肾素抑制剂ES - 1005不仅抑制血浆肾素活性,还抑制肾脏肾素的合成。