ROLE OF RENIN ISOELECTRIC HETEROGENEITY IN RENAL STORAGE AND SECRETION OF RENIN

Renin is a glycoprotein that is heterogeneous with respect to carbohyd rate content and net charge. In an attempt to clarify the role of reni n isoelectric heterogeneity in renal renin storage and secretion, the isoelectric profile of renal renin, secreted renin, and circulating re nin were directly assessed and compared under basal and stimulated con ditions by the use of an in vivo blood perfused rabbit kidney preparat ion. Under basal conditions, the kidney preferentially stored and secr eted the relatively basic isoelectric forms of renin. Acute stimulatio n of renin secretion (reduced renal perfusion pressure and angiotensin -converting enzyme inhibition) significantly increased the secretion o f the relatively basic isoelectric forms but had very little effect on the secretion of the relatively acidic renin forms. Circulating renin was composed primarily of relatively basic forms, which increased dis proportionately after stimulation of renin secretion. These findings s uggest that the isoelectric heterogeneity of renin is important in the cellular processing of renin and can be explained by a two-pool model in which the relatively acidic isoelectric forms of renin are constit utively secreted (and not stored) and the relatively basic isoelectric forms represent a regulated pathway in which they are stored and rapi dly released in response to acute secretory stimuli. Preferential hepa tic extraction of the more basic isoelectric forms has previously been described. Data from this study suggest that the disproportionate inc rease in circulating basic forms of renin observed after acute stimula tion reflects the net effect of preferential renal secretion and prefe rential hepatic degradation of the more basic renin isoelectric forms. The disproportionate increase in relatively basic circulating renin f orms after acute secretory stimulation results in an overall circulati ng renin activity with a shorter half-life.