Response of plasma prorenin and active renin to chronic and acute alterations of renin secretion in normal humans. Studies using a direct immunoradiometric assay.

Abstract

We employed a novel immunoradiometric assay to measure plasma levels of active renin and prorenin in physiologic and pharmacologic studies designed to characterize renin biosynthesis and processing in response to both chronic and acute stimuli of renin secretion in normal human subjects. Stimulation of renin secretion with prolonged dietary sodium restriction or amiloride resulted in marked increases in the plasma levels of prorenin, active renin, and plasma renin activity (PRA); suppression of renin secretion with indomethacin resulted in parallel decreases in prorenin, active renin, and PRA. In contrast, acute stimulation with upright activity or administration of an angiotensin-converting enzyme inhibitor, which increased active renin and PRA from 2-to 15-fold, had no effect on prorenin levels. Based on studies in cultured human juxtaglomerular tumor cells, it has been proposed that prorenin is secreted constitutively whereas active renin is stored in and released from secretory granules through a regulated pathway. Our studies are consistent with such a model: the parallel changes in active renin and prorenin with experimental maneuvers of long duration suggest that both the constitutive and regulated pathways are altered under these conditions. The increase in active renin levels in the absence of a change in prorenin that occurs in response to acute stimuli presumably represents the release of preformed active enzyme that is stored in secretory granules.

Comparative efficacy and safety of aliskiren and irbesartan in patients with hypertension and metabolic syndrome

“…Levels of prorenin were significantly increased from baseline to a similar extent with both irbesartan and aliskiren treatments, an expected consequence of any chronic stimulus of renin release. 30 Measurements of a large panel of biomarkers of inflammation and cardiovascular risk showed few statistically significant differences from baseline levels. Only the inflammatory mediator eotaxin 31 showed a statistically significant between-treatment difference, but the clinical significance of this finding is uncertain.…”

Multifunctional Actions of Approved and Candidate Stroke Drugs

“…Renin catalyzes the cleavage of angiotensinogen to angiotensin I, which in turn is cleaved by the angiotensin converting enzyme to its active form angiotensin II. 53,54 The appropriate stimulus for renin production by the kidney is glomerular hypoperfusion. 53 Angiotensin II acts via the specific angiotensin II receptors AT1 and AT2.…”

Local renin-angiotensin system in human adrenals and aldosteronomas.

“…The concentration of active renin was measured by an immunoradiometric assay kit (Diagnostics Pasteur, Marnes La Coquette, France) that uses two monoclonal antibodies against human renin (3E8 and 4G1), as previously described. 26 - 27 Briefly, the first antibody, 3E8, covalently linked to magnetic particles, binds both active and inactive renin, whereas the second antibody, 4G1, labeled with iodine-125, specifically recognizes active renin immobilized by 3E8. Antibody 4G1 did not bind 1) prorenin purified from human kidney or chorionic fluid, 2) prorenin produced by chorionic cells in culture, 3) six distinct synthesized renin fragments, or 4) related proteins such as pepsin or cathepsin D. 27 Immunoradiometric assay results were derived from a standard curve obtained by using monkey serum renin calibrated in Medical Research Council units.…”

“…26 - 27 Briefly, the first antibody, 3E8, covalently linked to magnetic particles, binds both active and inactive renin, whereas the second antibody, 4G1, labeled with iodine-125, specifically recognizes active renin immobilized by 3E8. Antibody 4G1 did not bind 1) prorenin purified from human kidney or chorionic fluid, 2) prorenin produced by chorionic cells in culture, 3) six distinct synthesized renin fragments, or 4) related proteins such as pepsin or cathepsin D. 27 Immunoradiometric assay results were derived from a standard curve obtained by using monkey serum renin calibrated in Medical Research Council units. The limit of detection was 5 pg/ml, the intra-assay coefficient of variation (CV) was 6% (n = 10), and the interassay CV was 10% (n=20).…”