Modification of glycosylation of renin in sodium-depleted and captopril-treated rats

Abstract

Concanavalin A (con A) chromatography of rat plasma revealed the presence of three differently glycosylated forms of renin, including the con A unbound form (renin C), the loosely bound form (renin A), and the tightly bound form (renin B). Rat renal cortical slices in vitro secreted all these forms. They had a different half-life in the plasma after ligation of both renal artery and vein (half-life of 21 +/- 1, 14 +/- 3, and 35 +/- 4 min for renin A, B, and C, respectively). Thus differently glycosylated forms of renin are released from the kidney into the blood circulation and disappear, with a different half-life. Rats were sodium-depleted and captopril-treated (40-60 mg.kg-1.day-1) for 2 wk, and the effects of these treatments on relative proportions of renin A, B, and C were investigated. These treatments elevated plasma renin concentration approximately 60-fold (from 24 +/- 3 to 1,406 +/- 128 ng angiotensin I.h-1.ml-1; P less than 0.01), in association with an increase in the relative percent of renin C in the plasma from 22 +/- 2 to 39 +/- 3% (P less than 0.01). Moreover, the relative proportion of renin C released from the renal cortical slices was significantly higher in the treated than in the control rats (42 +/- 9 vs. 16 +/- 3% of secreted renin, respectively; P less than 0.02). These results show that the predominant release of renin C, with the longest half-life (35 min) in the plasma, contributes to the increased plasma renin concentration in sodium-depleted and captopril-treated rats.

Adrenal and circulating renin-angiotensin system in stroke-prone hypertensive rats.

“…33 In brief, the samples of plasma and of renal and adrenal extracts were incubated with nephrectomized rat plasma containing an excess of renin substrate (2 /iM angiotensinogen), and the Ang I generated was measured by RIA.…”

“…33 After washing with 8 ml of the equilibration buffer, the column was eluted with the equilibration buffer containing 0.2 M a-methylmannoside. The flow rate was 12 ml/hr.…”

“…Furthermore, all these properties of adrenal active renin are similar to those observed for active renin from the kidney 31 -33 - 35 and plasma. 31 - 33 Thus, the increase in adrenal renin activity in SHRSP may be caused by the increased amount of active renin rather than the appearance of renin isoenzyme with higher enzymatic activity. This speculation is supported by the observation that the specific activity of adrenal renin from 25-week-old SHRSP was similar to that of renal renin.…”

Renal secretion and hepatic clearance of human multiple renin forms.

“…26 Because different isoelectric forms of renin exhibit pronounced differences in degradation rates in rats and dogs 1516 and in humans as reported in this study, it seems likely that the isoelectric heterogeneity of renin is due at least in part to differential glycosylation. Recent studies in rats have also suggested varying renal and brain effects of specific renin forms, 12 ' 13 differential blood pressure effects in stroke-prone hypertensive rats, 14 and differences in the renin form profile in Goldblatt hypertensive rats compared with control rats.…”

“…28 - 29 Renin glycosylation in the rat is associated with preferential renin degradation by the liver. 26 - 30 Therefore, it is likely that heterogeneous glycosylation of renin contributes to the differential hepatic clearance of the multiple renin forms. Because it is unknown whether isoelectric focusing distinguishes renin forms solely by their carbohydrate structure, these considerations may not fully explain the differential hepatic clearance of the renin forms.…”