Co-incubation of human saphenous vein segments with quinaprilat and the chymase inhibitor SBTI markedly reduced maximum contraction to angiotensin I (12.5 mN) compared to control (30.4 mN).
Demonstrates the existence of a chymase-dependent alternative pathway for angiotensin II formation in human saphenous veins that remains active during ACE inhibition.
Absolute Event Rate: 12.5% vs 30.4%
The aim of our study was to demonstrate the existence, location and functional importance of an alternative angiotensin II-forming pathway other than angiotensin converting enzyme (ACE) in the human saphenous vein (SV). 2. Vascular reactivity studies using an in vitro organ bath technique showed that the SV (n=20) produced similar maximum contractions in response to angiotensin I (41.5+/-5.4 mN) compared to those observed to angiotensin II (46.7+/-10.9 mN). The response to angiotensin I could be significantly inhibited (P<0.05) by incubation with the AT1 receptor antagonist losartan (1 microM). 3. Prior incubation of segments of SV with either captopril (1 microM) (n=6), quinaprilat (1 microM) (n=7), or the chymase inhibitor soya bean trypsin inhibitor (SBTI) (10 microM) (n=7) singularly failed to have any inhibitory effect on the response to angiotensin I. However when vessel segments (n=7) were co-incubated with quinaprilat (1 microM) and SBTI (10 microM), the SV exhibited a rightward shift in curve profile to angiotensin I and a markedly reduced maximum response 12.5+/-2.4 mN, when compared to control (30.4+/-7.6 mN), quinaprilat (24.5+/-9.4 mN), and SBTI (31.6+/-10.7 mN) on their own. 4. An immunohistochemical technique employing streptavidin biotin peroxidase localised ACE to both endothelial cells and smooth muscle cells while chymase was confined to mast cells in the adventitia of the vessel wall. 5. In conclusion, our results demonstrate the existence of an alternative angiotensin I converting pathway to that of ACE, involving chymase. Therefore, there is the capacity for a continuation of angiotensin II formation, in the presence of ACE inhibition.
Borland et al. (Thu,) reported a other. Quinaprilat and soya bean trypsin inhibitor (SBTI) co-incubation vs. Control was evaluated on Maximum contraction in response to angiotensin I. Co-incubation of human saphenous vein segments with quinaprilat and the chymase inhibitor SBTI markedly reduced maximum contraction to angiotensin I (12.5 mN) compared to control (30.4 mN).