ACE- versus chymase-dependent angiotensin II generation in human coronary arteries: A matter of efficiency?
Arteriosclerosis, Thrombosis, and Vascular Biology , Volume 23 - Issue 2 p. 251- 256
Objective - The objective of this study was to investigate ACE- and chymase-dependent angiotensin I-to-II conversion in human coronary arteries (HCAs). Methods and Results - HCA rings were mounted in organ baths, and concentration-response curves to angiotensin II, angiotensin I, and the chymase-specific substrate Pro11-D-Ala12-angiotensin I (PA-angiotensin I) were constructed. All angiotensins displayed similar efficacy. For a given vasoconstriction, bath (but not interstitial) angiotensin II during angiotensin I and PA-angiotensin I was lower than during angiotensin II, indicating that interstitial (and not bath) angiotensin II determines vasoconstriction. PA-angiotensin I increased interstitial angiotensin II less efficiently than angiotensin I. Separate inhibition of ACE (with captopril) and chymase (with C41 or chymostatin) shifted the angiotensin I concentration-response curve ≈5-fold to the right, whereas a 10-fold shift occurred during combined ACE and chymase inhibition. Chymostatin, but not captopril and/or C41, reduced bath angiotensin II and abolished PA-Ang I-induced vasoconstriction. Perfused HCA segments, exposed luminally or adventitially to angiotensin I, released angiotensin II into the luminal and adventitial fluid, respectively, and this release was blocked by chymostatin. Conclusions - Both ACE and chymase contribute to the generation of functionally active angiotensin II in HCAs. However, because angiotensin II loss in the organ bath is chymase-dependent, ACE-mediated conversion occurs more efficiently (ie, closer to AT1 receptors) than chymase-mediated conversion.
|Angiotensin, Angiotensin-converting enzyme, Chymase, Human coronary artery, Pro11-D-Ala12-angiotensin I|
|Arteriosclerosis, Thrombosis, and Vascular Biology|
|Organisation||Department of Cardio-Thoracic Surgery|
Tom, B, Garrelds, I.M, Scalbert, E, Stegmann, A.P.A, Boomsma, F, Saxena, P.R, & Danser, A.H.J. (2003). ACE- versus chymase-dependent angiotensin II generation in human coronary arteries: A matter of efficiency?. Arteriosclerosis, Thrombosis, and Vascular Biology, 23(2), 251–256. doi:10.1161/01.ATV.0000051875.41849.25