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  • Title: Dual inhibition of angiotensin converting enzyme and neutral endopeptidase by omapatrilat in rat in vivo.
    Author: Bäcklund T, Palojoki E, Grönholm T, Eriksson A, Vuolteenaho O, Laine M, Tikkanen I.
    Journal: Pharmacol Res; 2001 Nov; 44(5):411-8. PubMed ID: 11712872.
    Abstract:
    The pharmacological profile of a vasopeptidase inhibitor is dependent on the ratio of neutral endopeptidase (NEP)vs angiotensin converting enzyme (ACE) inhibition of the particular drug. We used in vitro autoradiography to determine the local renal and cardiac NEP and ACE inhibition after oral treatment with the dual NEP/ACE inhibitor omapatrilat in rat. Maximal inhibition of both renal NEP and ACE was achieved at the omapatrilat dose of 40 mg kg(-1)day(-1). Effective local ACE inhibition was detected also in the myocardium. The haemodynamic effects were similar to captopril, but omapatrilat treatment produced more favorable effect on natriuretic peptide levels. In conclusion, good tissue penetration of omapatrilat and balanced NEP/ACE inhibition may prove to be useful in the treatment of hypertension and heart failure.
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