RENIN-LIKE ENZYMES IN HUMAN VASCULATURE

The present study was designed to identify angiotensin I (Ang I)-forming angiotensinogenases in human extrarenal vasculature and to examine the theory of Jimenez DEas on their stimulation in essential hypertension. Vascular sections obtained intraoperatively from 14 normotensive and 16 hypertensive patients undergoing corrective surgery, 68 umbilical cord blood vessels from parturient women, tissue samples from nine explanted hearts, and serum from anephric and healthy individuals were investigated. Ang 1-forming anglotensinogenase activities were determined enzyme-kinetically by using Ang 1 radioimmunoassay and purified sheep or human angiotensinogens. Three nonrenin Ang 1-fonning angiotensinogenases (pH optima of 4.0, 5.1, and 6.1) were identified in extrarenal vasculature, in cardiac tissues, and in plasma. Highest specific activities of nonrenin Ang 1-forming angiotensinogenase (in nano-grams Ang 1 per gram times hour; mean±SD) were found in cardiac tissue (2, 821±497, n=9), followed by carotid artery intima (1, 448 ±982, n = 10), arteries (1, 307 ± 736, n = 18), and umbilical cord arteries (135±55, n=35). Extrarenal arterial Ang I-forming angiotensinogenases were linearly correlated with those of local angiotensin converting enzyme and plasma renin activity. In essential hypertension, extrarenal arterial Ang I-forming angiotensinogenases were scattered, but not generally stimulated. The data obtained indicate the existence of nonrenin Ang I-forming angiotensinogenases in human extrarenal vasculature, in kidney, and in plasma. The postulate of stimulation of extrarenal arterial Ang I-formlng angiotensinogenases in essential hypertension cannot be supported. Similar to the classification of plasma renin activity, a classification of Ang I-forming angiotensinogenase activity is proposed, consisting of patients with essential hypertension divided into subgroups exhibiting high, normal, or low vascular Ang I-formlng angiotensinogenase activities. © 1990 American Heart Association, Inc.