Effects of renin inhibitors on the expression of kidney renin gene and tissue renin-like activity

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The effect of renin inhibitor ES-1005 on renin gene expression was investigated in sodiumdepleted marmosets. The kidneys were removed after continuous infusion of ES-1005 (12mg/kg perh) for 2h. The relative amount of kidney renin messenger (m)RNA was measured by densitometric Northern blot analysis using an α-32P-iabelled human renin complementary (c)DNA fragment as a hybridization probe. Plasma renin activity was completely inhibited by ES-1005. The level of kidney renin mRNA decreased significantly to about onethird of the normal control value. We also investigated the inhibitory potency of the renin inhibitor ES-6864 on the renin-like activity in dog tissues (adrenal glands, aorta and brainstem). ES-6864 inhibited the tissue renin-like activity with an IC50 of 10 -7 to 10-8mol/l in vitro. Renin inhibitors not only inhibit the activity of plasma and tissue renin, but also suppress the synthesis of renin in the kidney.

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