Abstract
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.
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