Mammalian inhibitors of angiotensin converting enzyme (kininase II)

Urines and sera (human, guinea pig and rat) contain low molecular weight inhibitors of angiotensin converting enzyme (ACE). The urines contain ACE, but the enzyme is scarcely measurable without prior ultrafiltration or dialysis. The activity increases strikingly through three ultrafiltration steps using a membrane with a 10,000 MW retention limit. As implied, the ultrafiltrates contain inhibitory activity and can prevent the hydrolysis of [3H]benzoyl-Gly-His-Leu by ACE from any source, including lung and serum. Human urinary ultrafiltrate contains at least three inhibitors separable on Bio-Gel P-2. The inhibitors are acidic and can be partially purified on Bio-Rex 70 developed with an acetic acid gradient. The smallest of the inhibitors can be purified to apparent homogeneity by partition chromatography (sephadex G-25; butanol, acetic acid, H2O; 4:1:5). The excretion of inhibitory activity varies in response to dietary salt: Activity is low when rats are maintained on a high NaCl diet and is high (3 x's control) on a low NaCl diet. Thus, the activity of ACE may be modulated in vivo by naturally-occurring enzyme inhibitors. Whether some hypertensive patients are deficient in ACE inhibitory activity remains to be determined.