Role of renin isoelectric heterogeneity in renal storage and secretion of renin.
Renin is a glycoprotein that is heterogeneous with respect to carbohydrate content and net charge. In an attempt to clarify the role of renin isoelectric heterogeneity in renal renin storage and secretion, the isoelectric profile of renal renin, secreted renin, and circulating renin were directly assessed and compared under basal and stimulated conditions by the use of an in vivo blood perfused rabbit kidney preparation. Under basal conditions, the kidney preferentially stored and secreted the relatively basic isoelectric forms of renin. Acute stimulation of renin secretion (reduced renal perfusion pressure and angiotensin-converting enzyme inhibition) significantly increased the secretion of 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 disproportionately after stimulation of renin secretion. These findings suggest 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 constitutively secreted (and not stored) and the relatively basic isoelectric forms represent a regulated pathway in which they are stored and rapidly released in response to acute secretory stimuli. Preferential hepatic extraction of the more basic isoelectric forms has previously been described. Data from this study suggest that the disproportionate increase in circulating basic forms of renin observed after acute stimulation reflects the net effect of preferential renal the more basic renin isoelectric forms. The disproportionate increase in relatively basic circulating renin forms after acute secretory stimulation results in an overall circulating renin activity with a shorter half-life.
Opsahl
J A
JA
School of Medicine, University of Minnesota, Minneapolis, MN.
Abraham
P A
PA
Shake
J G
JG
Katz
S A
SA
D000818:Animals; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D007525:Isoelectric Focusing; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D010477:Perfusion; D011312:Pressure; D011817:Rabbits; D012079:Renal Circulation; D012083:Renin / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism
D004656:Enalapril; D012083:Renin