Dual pathway for angiotensin II formation in human internal mammary arteries.
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 microM captopril inhibited slightly the response to angiotensin I (pD2 from 7.09+/-0.11-6.79+/-0.10, P<0.001), while 100 microM captopril nearly abolished the response to [pro10] 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 pD2 of angiotensin I similar to captopril was observed in the presence of 50 microM chymostatin (pD2 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.
Voors
A A
AA
Department of Clinical Pharmacology, University of Groningen, The Netherlands.
Pinto
Y M
YM
Buikema
H
H
Urata
H
H
Oosterga
M
M
Rooks
G
G
Grandjean
J G
JG
Ganten
D
D
van Gilst
W H
WH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000803:Angiotensin I / Q000378:metabolism* / Q000502:physiology; D000804:Angiotensin II / Q000096:biosynthesis* / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008323:Mammary Arteries / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000187:drug effects; D014661:Vasoconstriction
D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D000804:Angiotensin II; D000803:Angiotensin I; C002101:chymostatin; D002216:Captopril