METABOLISM OF ANGIOTENSIN-II AND SOME ANALOGS IN INTACT STRIPS AND IN MUSCLE PREPARATIONS OF RABBIT AORTAE

The purpose of this work was twofold: (a) to develop a muscle preparation of the rabbit aorta free of adventitia and endothelium, and (b) to measure the metabolism of angiotensin II (AT(II)) in this preparation. The muscle was prepared by 'shucking-off' the adventitia layer and by eliminating the endothelium. Concentration-response curves to AT(II) and noradrenaline (NA) measured in the muscle preparation provided pD2 values for AT(II) and NA not significantly different from those observed in the intact aortic strip. However, the maximal tension developed by the two agonists averaged 20-30% of the maximal tension of the intact strips. Apparent diffusion of AT(II), in and out of the tissue, was faster in the muscle while NA diffusion was not significantly different. Metabolism of AT(II) was measured at the plateau of contraction and after complete relaxation in both the muscle and the intact strip. Ten percent of AT(II) was metabolized at the plateau of the contraction and 50% after complete relaxation. Heptapeptide 1-7 was the metabolite found in both preparations. 1-β-Asp AT(II) was also broken down to heptapeptide 1-7 while 1-β-Asp,8-Phe-OMe-AT(II) resisted the degradation and was found unchanged even after 90 min of incubation. It is suggested that the enzyme which inactivates AT(II) is located in the smooth muscle cells and that it is a carboxypeptidase.