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- W73202910 abstract "Angiotensin converting enzyme inhibitors (ACEi) and dual acting ACEi-neprilysin (NEP) inhibitors are associated with risk of angioedema in the clinic. In the present study, we used a rodent model to assess the angioedema risk of administration of angiotensin receptor blocker (ARB) and NEP inhibitor, dosed alone or in combination, at antihypertensive doses. Intravenous effects (mg/kg) of ACEi (lisinopril, LIS 0.03-10), ACEi-NEPi (omapatrilat, OMPT-0.03-10; ilepatril, ILPT-0.3-30), AT1 antagonist (valsartan VAL-0.3-10), neprilysin inhibitor (CGS-24592, CGS-0.3-30) or a combination (AT1-NEPi) and vasodilator- sodium nitroprusside (SNP) on tracheal plasma extravasation (TPE) was tested in anesthetized rat (Sulpizio et al., JPET 309:1411,2004). Treatment with LIS, OMPT, ILPT or ACEi-NEPi (LIS + CGS) resulted in a significant, dose related increases in TPE (peak values 48, 91, 89 and 57 ng/mg respectively vs. 1-10 ng/mg, vehicle). Pretreatment with HOE 140 (bradykinin B2 antagonist, 30 ìg/kg, iv) completely antagonized TPE observed with LIS, OMPT and ILPT. In contrast, VAL, CGS, VAL+CGS combination or SNP treatment produced no increase in TPE. These results indicate that unlike ACEi or ACEi-NEPi, ARB or ARB-NEPi did not result in increased TPE (hence carry minimal or no risk of angioedema). Additionally, bradykinin mediated angioedema risk can be reliably detected pre-clinically using this simple assay." @default.
- W73202910 created "2016-06-24" @default.
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- W73202910 date "2009-04-01" @default.
- W73202910 modified "2023-09-27" @default.
- W73202910 title "Comparative preclinical assessment of angioedema risk of inhibitors of renin‐angiotensin system and neprilysin in the anesthetized rat tracheal plasma extravasation assay" @default.
- W73202910 doi "https://doi.org/10.1096/fasebj.23.1_supplement.lb379" @default.
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