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Differential effects of ACE and chymase in the metabolism of exogenous angiotensin‐(1–12) in Wistar‐Kyoto rats
Author(s) -
Moniwa Norihito,
Varagic Jasmina,
Ahmad Sarfaraz,
Ferrario Carlos M.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1105.3
Subject(s) - chymase , endocrinology , medicine , angiotensin ii , chemistry , saline , renin–angiotensin system , lisinopril , angiotensin converting enzyme , enzyme , receptor , blood pressure , biochemistry
We examined whether angiotensin converting enzyme (ACE) or chymase is involved in the processing of angiotensin‐(1–12) [Ang‐(1–12)] in the circulation of 15 male anesthetized Wister‐Kyoto rats (WKY) at age 12–13 weeks. Rats were assigned to vehicle (Veh, saline, n=6), lisinopril (Lis, 10mg/kg, n=5) or chymostatin (10mg/kg, n=4). The saline Veh or Lis were infused intravenously 15 min prior to the administration of Ang‐(1–12) while the chymase inhibitor was administered intraperitoneally 30 min prior to Ang‐(1–12). Plasma Ang‐(1–12), Ang I, Ang II, and Ang‐(1–7) levels were measured by RIA. Peak plasma Ang‐(1–12) levels at 15 min following initiation of the infusion were not statistically different among the three treated groups while in Lis‐treated rats plasma Ang I levels rose to 3.1 versus 1.6 pmol/mL in Veh and plasma Ang II decreased to 0.3 compared with 15.2 pmol/mL in Veh. Although inhibition of chymase had no significant effect on plasma levels of Ang I and Ang II, peak concentrations of circulating Ang‐(1–7) rose to 0.75 compared with 0.43 and 0.47 pmol/mL in Veh and Lis‐treated WKY, respectively (p < 0.05). We conclude that angiotensin converting enzyme acts as the primary source for the conversion of Ang‐(1–12) in the circulation of WKY and also show for the first time a role for chymase in Ang‐(1–7) production from Ang‐(1–12). This research was supported by PO1 HL 051952.