Alternative pathways of angiotensin II production in the human saphenous vein

1 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). 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 AT(1) receptor antagonist losartan (1 mu M). 3 Prior incubation of segments of SV with either captopril (1 mu M) (n=6), quinaprilat (1 mu M) (n=7), or the chymase inhibitor soya bean trypsin inhibitor (SBTI) (10 mu M) (n=7) singularly failed to have any inhibitory effect on the response to angiotensin I. However when vessel segments (n=7) were coincubated with quinaprilat (1 mu M) and SBTI (10 mu M), 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.