Plasma Angiotensinase Activity in Cirrhosis. ∗

Abstract

Plasma angiotensinase activity is of theoretic interest in cirrhosis for several reasons. If such enzymatic activity reflects production of angiotensin(l) and thus aldosterone(2), increased activity would be expected in association with secondary hyperaldosteronism, as manifested by ascites and edema. Moreover, as activation of the renin-angiotensin-aldosterone system may result from decreased renal perfusion(2,3), plasma angiotensinase activity could be augmented by renal circulatory failure(4) in hepatic disease. An alternative suggestion is that, like other enzymes, angiotensinases might be released from the liver in abnormally great amounts as a result of hepatic injury(5), regardless of changes in production of angiotensin. Under such circumstances, the resulting acceleration of angiotensin degradation could contribute to the infrequency with which hypertension is said to occur in patients with cirrhosis (6,7) and might explain the reduced pressor responsiveness to angiotensin described in this disease(8).

The degradation of angiotensin has been studied in hypertension(1,9,10), edema(1), pregnancy (1,11), and toxemia (1,12). The conflicting results could come in part from use of assay methods based on different principles, namely, removal of radioactive iodine from the angiotensin molecule (10), destruction of its pressor activity(1), and release of valine measured by colorimetry (12). When the last method was applied to patients with various diseases (11), particularly high values were found in those with hepatobiliary disorders. Since the authors did not equate the rate of liberation of valine with the rate of pressor degradation, a biologic assay of angiotensinase activity in patients with cirrhosis seemed more desirable from the physiologic point of view.

Angiotensinase activity appears to have some substrate specificity, since plasma does not destroy the pressor activity of β-aspartyl angiotensin (13) nor does it inactivate arginyl¹ angiotensin, deaminoangiotensin or poly-O-acetylseryl angiotensin (14). The optimal pH and some ionic requirements are known. Klaus and associates (12) considered an as-partic acidaminopeptidase system responsible but conceded the participation of other aminopeptidases. However, a specific enzyme has not yet been identified. It is necessary, therefore, to refer to “plasma angiotensinase activity” until further purification reveals the peptidase system(s) responsible.