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Dual pathway for angiotensin II formation in human internal mammary arteries
Author(s) -
Voors Adriaan A.,
Pinto Yigal M.,
Buikema Hendrik,
Urata Hidenori,
Oosterga Margreeth,
Rooks Gerrit,
Grandjean Jan G.,
Ganten D,
Van Gilst Wiek H.
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702150
Subject(s) - captopril , chymase , angiotensin ii , angiotensin converting enzyme , renin–angiotensin system , medicine , endocrinology , ace inhibitor , chemistry , coronary arteries , contraction (grammar) , enzyme , artery , receptor , biochemistry , blood pressure
1 Angiotensin converting enzyme (ACE) is thought to be the main enzyme to convert antiotensin I to the vasoactive angiotensin II. Recently, in the human heart, it was found that the majority of angiotensin II formation was due to another enzyme, identified as human heart chymase. In the human vasculature however, the predominance of either ACE or non‐ACE conversion of angiotensin I remains unclear. 2 To study the effects of ACE‐ and chymase‐inhibition on angiotensin II formation in human arteries, segments of internal mammary arteries were obtained from 37 patients who underwent coronary bypass surgery. 3 Organ bath experiments showed that 100 μ M captopril inhibited slightly the response to angiotensin I (pD 2 from 7.09±0.11–6.79±0.10, P <0.001), while 100 μ M captopril nearly abolished the response to [pro 10 ] angiotensin I, a selective substrate for ACE, and the maximum contraction was reduced from 83±19%–23±17% of the control response ( P =0.01). A significant decrease of the pD 2 of angiotensin I similar to captopril was observed in the presence of 50 μ M chymostatin (pD 2 from 7.36±0.13–6.99±0.15, P <0.039), without influencing the maximum response. In the presence of both inhibitors, effects were much more pronounced than either inhibitor alone, and a 300 times higher dose was needed to yield a significant contraction response to angiotensin I. 4 These results indicate the presence of an ACE and a non‐ACE angiontensin II forming pathway in human internal mammary arteries.British Journal of Pharmacology (1998) 125 , 1028–1032; doi: 10.1038/sj.bjp.0702150