Modification of the enzymatic activity of renin by acidification of plasma and by exposure of plasma to cold temperatures.

Abstract

SUMMARY Plasma renin activity (PRA) increases after acidification of plasma or exposure of plasma to cold temperatures. The purpose of the present study is to evaluate the hypothesis that these increases of PRA reflect inactivation of circulating renin inhibiting factors. In each of eight normotensive subjects, mean PRA increased (p < 0.01) after acidification of plasma by acid dialysis (98%), after acidification of plasma by addition of HCI (47%), or after exposure of plasma to -4°C for 5 days (155%). Renin substrate-free plasma was obtained by passing plasma over Sephadex G-50-40. Both untreated plasma and the substrate-free extract of plasma inhibited the enzymatic activity of renin (p < 0.01); little or no inhibition occurred after addition of acidified plasma or the protein-free extract of acidified plasma to renin-renin substrate. After addition of exogenous renin to cold-exposed plasma, the rate of angiotensin I generation was greater than that in control plasma (p < 0.05), although renin substrate did not differ. These observations suggest that denaturation of a circulating renin inhibitor may contribute to increased PRA after acidification or cold exposure of plasma. In a separate experiment, the addition of polyunsaturated free fatty acids (linoleic and arachidonic) to renin-renin substrate inhibited angiotensin production, although no inhibition occurred after dialysis of these fatty acids against an acid buffer (pH 3.3). Prolonged exposure of linoleic acid to cold temperatures did not affect its capacity to inhibit renin. Thus, loss of long chain, unSaturated free fatty acids may contribute to increased PRA after acid dialysis of plasma but not to increased PRA after exposure of plasma to cold temperatures. RENIN is a proteolytic enzyme that cleaves a circulating alpha-2-globulin substrate to form the decapeptide angiotensin I. Several reports suggest that plasma contains inhibitors of the reaction between renin and its substrate.19 Acetonesoluble neutral lipids extracted from plasma inhibit renin, 10 and we have recently demonstrated that physiologic concentrations of long chain, unsaturated fatty acids inhibit both the capacity of renin to. generate angiotensin in vitro and the pressor response to renin in vivo.11 Thus, in addition to renin and renin substrate concentrations, the measurement of plasma renin activity (PRA) may be affected by circulating renin inhibitors. We have used the term renin reactivity to refer to the capacity of added renin to generate angiotensin I either after its addition to crude

Characterization of inactive renin ("prorenin") from renin-secreting tumors of nonrenal origin. Similarity to inactive renin from kidney and normal plasma.

“…Inactive renin has several characteristics of a biosynthetic precursor of renin (8,12,13). Other evidence has been cited to support the view that it may be a postsynthetic modification ofactive renin (15)(16)(17), especially since, in renal cortical extracts from several species, renin can form a large molecular weight complex with a polypeptide binding substance (18)(19)(20). However, these complexes are enzymatically active and thus differ from the completely inactive substance found in human plasma (8).…”