Elastase ‐2, an angiotensin II‐generating enzyme, contributes to increased Ang II in resistance arteries of mice with myocardial infarction.

Abstract Angiotensin II (Ang II), whose generation largely depends on angiotensin‐converting enzyme activity, mediates most of the renin‐angiotensin‐system effects. Elastase‐2 (ELA‐2), a chymotrypsin‐serine protease elastase family member 2A, alternatively generates Ang II in rat arteries. Myocardial infarction (MI) leads to intense RAS activation, but mechanisms involved on Ang II‐generation in resistance arteries are unknown. We hypothesized that ELA‐2 contributes to vascular Ang II generation and to cardiac damage in mice submitted to MI. Concentration‐effect curves to Ang I and Ang II were performed in mesenteric resistance arteries from male wild type (WT) and ELA‐2 knockout (ELA‐2KO) mice submitted to left anterior descending coronary artery ligation (myocardial infarction, MI). MI size was similar in WT (29.5 ± 9 %) and ELA‐2KO (32 ± 4%) mice. Ejection fraction and fractional shortening after MI similarly decreased in both strains. However, MI decreased stroke volume and cardiac output in WT, but not in ELA‐2KO mice. Ang I‐induced contractions increased in WT mice submitted to MI (MI‐WT) compared to Sham‐WT mice. No differences were observed in Ang I reactivity between arteries from Sham‐ELA‐2KO and ELA‐2KO submitted to MI (MI‐ELA‐2KO). Ang I contractions increased in arteries from MI‐WT vs. MI‐ELA‐2KO mice. Chymostatin attenuated Ang I‐induced vascular contractions in WT mice (P < 0.05), but did not af...
Source: British Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: RESEARCH PAPER Source Type: research