New renin--angiotensin from plasma prorenin?
Within 24 h of binephrectomy in rats, plasma prorenin (activated by trypsin) rose well above normal levels while renin disappeared. This rise in prorenin may be attributed to enhanced secretion by an unidentified extrarenal source and the lack of any renin formation from it suggests that nephrectomy abolishes any systemic "convertase" mechanism that exists for its activation. Within 48 h of adrenalectomy in rats, plasma prorenin levels dropped below normal, while renin rose sharply, suggesting enhanced activation of prorenin to renin, resulting in prorenin depletion, and/or the release of a higher proportion of renin: prorenin by the kidneys. To test for enhanced convertase activity, we crosscirculated adrenalectomized (high convertase) and nephrectomized (low convertase) rats and observed a rapid drop in prorenin with an increase in renin in their shared blood. This was also observed after mixing their bloods in vitro, without crosscirculation, indicating that renal convertase activity was in the bloodstream and not just in the kidneys. Acute nephrectomy of previously adrenalectomized rats lowered renin and raised prorenin within 15 min suggesting a rapid loss of kidney-derived convertase. These results could not be attributed to changes in renin-substrate concentration. The new renin (from activated extrarenal prorenin) was blocked by a monoclonal antibody effective against normal rat plasma renin. It also generated immunoreactive angiotensin I, indicating immunological and biological coidentity with renal renin. The blood of normal control rats did not exhibit convertase activity in vivo or in vitro. These data point to a secretory (endocrine) source of extrarenal prorenin which is stimulated by nephrectomy and to a renal prorenin convertase mechanism which is abolished by nephrectomy and stimulated by adrenalectomy. Thus, in a high renin state, active renin may arise by activation of circulating prorenin (renal and extrarenal) as well as by direct renal release.
Hare
G M
GM
Department of Physiology, University of Toronto, Ontario, Canada.
Osmond
D H
DH
D000315:Adrenalectomy; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003427:Cross Circulation / Q000379:methods; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000097:blood*; D007668:Kidney / Q000201:enzymology; D008297:Male; D009392:Nephrectomy; D051381:Rats; D012083:Renin / Q000097:blood* / Q000276:immunology
D000911:Antibodies, Monoclonal; D004792:Enzyme Precursors; D012083:Renin