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Human renin inhibiting dipeptide.

N Toda, M Miyazaki, Y Etoh

    European Journal of Pharmacology
    |October 7, 1986
    PubMed
    Summary

    KRI-1177, a novel compound, effectively inhibits renin activity, particularly in primates. This selective inhibition leads to reduced blood pressure and angiotensin levels, suggesting potential therapeutic applications for hypertension.

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    Area of Science:

    • Pharmacology
    • Cardiovascular Research
    • Biochemistry

    Background:

    • Renin is a key enzyme in the renin-angiotensin-aldosterone system (RAAS), regulating blood pressure.
    • Inhibition of renin activity is a therapeutic strategy for managing hypertension.

    Purpose of the Study:

    • To investigate the inhibitory effects of KRI-1177, a nor-statine dipeptide, on renin activity.
    • To determine the selectivity of KRI-1177's inhibition across different species.
    • To evaluate the in vivo effects of KRI-1177 on blood pressure and RAAS components.

    Main Methods:

    • In vitro assays measuring renin activity in plasma from various species (human, monkey, dog, rabbit, rat).
    • Intravenous administration of KRI-1177 to anesthetized monkeys.
    • Measurement of systemic blood pressure, plasma renin activity, and angiotensin concentrations post-administration.

    Main Results:

    • KRI-1177 markedly inhibited renin activity in human and Japanese monkey plasma compared to other species.
    • Intravenous KRI-1177 administration lowered systemic blood pressure in monkeys.
    • Plasma renin activity and angiotensin concentrations were reduced following KRI-1177 injection.

    Conclusions:

    • KRI-1177 demonstrates selective inhibition of primate renin activity.
    • The compound effectively reduces blood pressure and RAAS activity in vivo.
    • KRI-1177 shows potential as a hypotensive agent targeting primate renin.

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