FUNCTIONAL-ROLE OF CHYMASE IN ANGIOTENSIN-II FORMATION IN HUMAN VASCULAR TISSUE

Recent reports suggested that human heart chymase contributed little t o angiotensin (Ang) II formation in the presence of natural protease i nhibitors such as a-antitrypsin. We studied whether chymase could cont ribute to Ang II formation in the presence of natural protease inhibit ors in the homogenate, the extract, and slices of human vascular tissu e, and whether these inhibitors affect Ang I-induced vasocontractile r esponses due to chymase. In the homogenate, lisinopril, chymostatin, a nd 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-antihypsin was 18, 94, and 93%, respectively. In the slices, lisinopril and chymostatin inhibited Ang II formation by 5 and 90%, respectively. However, unlike the homogenat e and the extract experiments, only 8% of the Ang LI formation was sup pressed 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 b locking Ang I-induced vasoconstriction in the presence of lisinopril, which demonstrates that Ang II formation is dependent on chymase. Thes e findings suggest that chymase in human vascular tissue plays a funct ional role in Ang II formation in the presence of natural protease inh ibitors such as alpha-antitrypsin.