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Angiotensin‐(1–7) augments endothelium‐dependent relaxations of porcine coronary arteries to bradykinin by inhibiting ACE1
Author(s) -
Vanhoutte Paul Michel,
Wu Dongmei,
Khang Gilson,
Raffai Gabor
Publication year - 2013
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.27.1_supplement.878.3
Subject(s) - bradykinin , angiotensin ii , chemistry , captopril , angiotensin converting enzyme , medicine , renin–angiotensin system , endocrinology , vasodilation , endothelium , receptor , activator (genetics) , icatibant , vasoconstriction , pharmacology , blood pressure , biochemistry
Angiotensin converting enzyme 2 (ACE2) converts angiotensin II to angiotensin‐(1–7) that activates Mas receptors, inhibits ACE, modulates bradykinin (BK) receptor sensitivity. The present study compared the direct and indirect (on the response to BK) effect(s) of the ACE2 activator diminazene aceturate (DIZE) and angiotensin‐(1–7) in rings of isolated porcine coronary arteries, with or without endothelium, suspended in conventional organ chambers for isometric tension recording. In preparations contracted with U46619 (10 −7 M), increasing concentrations of DIZE, angiotensin‐(1–7) or of the ACE inhibitor captopril, did not cause significant changes in tension before or after desensitization of BK receptors. B K caused concentration‐dependent and endothelium‐dependent relaxations which were inhibited partially by L‐NAME or TRAM‐34 plus UCL‐1684, but not by indomethacin. The response to BK was not affected by DIZE, but significantly potentiated, to a similar extent, by angiotensin‐(1–7) and captopril. The two compounds augmented the response in the presence of either L‐NAME or TRAM‐34 plus UCL‐1684, indicating potentiation of NO bioavailability and endothelium‐dependent hyperpolarizations, respectively. These results indicate that in coronary arteries angiotensin‐(1–7) enhances both endothelium‐dependent relaxations and hyperpolarization to bradykinin solely by ACE inhibition. Research support: World Class University program (R31–20029), Ministry of Education, Science and Technology, South Korea.