Asynchronous changes in prorenin and renin secretion after captopril in patients with renal artery stenosis.

Abstract

SUMMARY An assay of plasma prorenin was developed in which the conversion to renin occurred under apparently optimal conditions. Some characteristics of the assay were 1) prorenin was activated by Sepharose-bound trypsin at 4°C; 2) the concentration of activator was not critical provided that incubation was prolonged until renin activity had reached a plateau; and 3) this plateau was stable and had the same height as after maximal activation with acid, pepsin, plasmin or urokinase. Maximal activity with Sepharose-bound trypsin at 4°C was higher than with cryoactivation, and optimal conditions were more readily reproduced than with trypsin at 37°C or with acid-activation. The assay was used for measurements in peripheral and renal vein plasma after captopril in hypertensive patients with unilateral renal artery stenosis. Peripheral renin rose within 30 minutes after a first dose of captopril, 50 mg orally, and it remained high with chronic treatment. In contrast, peripheral prorenin fell initially and rose after 4 hours. These changes in peripheral plasma were related to changes in the secretion rates of the two forms of renin from the affected kidney. Thus chronic, but not acute, stimulation of renin release was associated with an increased secretion rate of prorenin. The late rise in prorenin is probably an indication of enhanced synthesis in the kidney, so that more prorenin is available for conversion. The data suggest that prorenin is indeed a biosynthetic precursor of renin and that, at least under certain circumstances, a major proportion of circulating prorenin originates from the kidney. (Hypertension 5: 244-256, 1983) KEY WORDS • captopril • converting enzyme • prorenin renal artery stenosis * renin A BOUT 80% of the renin in normal human plasma is thought to circulate in an inactive form.

Beneficial Effects of Adding Spironolactone to Recommended Antihypertensive Treatment in Diabetic Nephropathy

“…Blood samples for plasma renin activity and aldosterone concentrations were taken after 30 min of supine rest. Plasma renin activity was measured by a method based on determining by radioimmunoassay the amount of angiotensin I generated; normal range is 1-12 ng angiotensin I ml Ϫ1 h Ϫ1 (17). Plasma aldosterone was measured with a radioimmunoassay (Coat-aCount; Diagnostic Products, Los Angeles, CA); normal range was 50 -250 pg/ml.…”

The changes in active and inactive renin induced by various maneuvers in hypertensive patients.

“…Some authors reported the reciprocal change in active and inactive renin in normal subject (Goldstone et al 1983) and EH or RVH (Glorisso et al 1982;Derkx et al 1983). But others observed no change in inactive renin accompanying an increase in active renin in normal subjects (Millar et al 1980) and in patients with EH or RVH (Linjin et al 1980;Sealey et al 1981).…”

Biochemical, Structural and Pathophysiological Aspects of Prorenin and (Pro)renin Receptor

“…Renin and prorenin have long been considered as the separate mediators of tissue and circulating systems (Sealy & Rubattu, 1989). In vitro, when prorenin is acidified at pH 3.3 or exposed to low temperature (< 4˚C) or allowed to interact with antibodies designed from its prosegment sequences (protein-protein interaction), it mediates intrinsic catalytic activity without removal of the prosegment sequence from its N-terminus through a reversible change in conformation (Derkx et al, 1979(Derkx et al, , 1983(Derkx et al, , 1987a(Derkx et al, & b, 1992Pitarresi et al, 1992, Suzuki et al, 2000.…”