Evidence for a potent angiotensin I degrading enzyme different from angiotensin I converting enzyme in rat vascular tissues.
There are indications for the existence of an intrinsic renin angiotensin system in vascular walls, which is assumed to participate in blood pressure regulation and in pathogenesis of arterial hypertension. It was evaluated if and to what extent the decapeptide angiotensin (A) I, one of the natural substrates of A I converting enzyme (ACE), is degraded by other peptidases than ACE in rat vascular tissues. A I and A II degradation was studied in arterial and venous vascular wall extracts. The activities ranged between 0.068 +/- 0.025 U and 0.044 +/- 0.025 U. The enzymes involved were biochemically characterized by determination of isoelectric points (pI), pH optima, molecular weights and by investigation of their inhibition behavior in vitro. One potent A I degrading enzyme (AIDE) was identified with pI between 3.6 and 3.9, and pH optimum at 7.75. In vitro studies revealed that AIDE activity was not blocked by the specific ACE inhibitors MK 421 or MK 422 (both 11 nMol/ml). The molecular weight of AIDE ranged between 440,000 and 457,000. The results indicate that AIDE is not identical to ACE (pI 4.2-5.0; pH optimum 8.3). AIDE was also observed in aortic smooth muscle cells cultured in vitro. AIDE decreased following bilateral nephrectomy or administration of aldosterone combined with sodium chloride loading, whereas it was elevated in spontaneously hypertensive rats (Okamoto strain). Since AIDE metabolizes A I, one of the substrates of ACE, it may indirectly affect A II formation and bradykinin inactivation as well.
D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology*; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System; D014684:Venae Cavae / Q000201:enzymology*
D000450:Aldosterone; D010450:Endopeptidases; D007703:Peptidyl-Dipeptidase A; C051318:angiotensin I degrading enzyme