Functional Role of Chymase in Angiotensin II Formation in Human Vascular Tissue

Recent reports suggested that human heart chymase contributed little to angiotensin (Ang) II formation in the presence of natural protease inhibitors such as alpha-antitrypsin. We studied whether chymase could contribute to Ang II formation in the presence of natural protease inhibitors in the homogenate, the extract, and slices of human vascular tissue, and whether these inhibitors affect Ang I-induced vasocontractile responses due to chymase. In the homogenate, lisinopril, chymostatin, and alpha-antitrypsin inhibited the formation of Ang II by 14, 92, and 74%, respectively. In the extract, the inhibition of Ang II formation by lisinopril, chymostatin, and alpha-antitrypsin was 18, 94, and 93%, respectively. In the slices, lisinopril and chymostatin inhibited Ang II formation by 5 and 90%, respectively. However, unlike the homogenate and the extract experiments, only 8% of the Ang II formation was suppressed by alpha-antitrypsin. In isolated human gastroepiploic artery, 30% of Ang I-induced vasoconstriction was blocked by lisinopril, and the rest was completely eliminated by a combination of lisinopril and chymostatin. On the other hand, alpha-antitrypsin was ineffective in blocking Ang I-induced vasoconstriction in the presence of lisinopril, which demonstrates that Ang II formation is dependent on chymase. These findings suggest that chymase in human vascular tissue plays a functional role in Ang II formation in the presence of natural protease inhibitors such as alpha-antitrypsin.