Hare G M, Osmond D H
Department of Physiology, University of Toronto, Ontario, Canada.
Am J Hypertens. 1990 Mar;3(3):196-203. doi: 10.1093/ajh/3.3.196.
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.
大鼠双侧肾切除术后24小时内，血浆中（经胰蛋白酶激活的）肾素原水平升至远高于正常水平，而肾素消失。肾素原水平升高可能归因于未明确的肾外来源分泌增强，且未从中形成任何肾素，这表明肾切除消除了任何存在的使其激活的全身“转化酶”机制。大鼠肾上腺切除术后48小时内，血浆肾素原水平降至正常以下，而肾素急剧上升，提示肾素原向肾素的激活增强，导致肾素原耗竭，和/或肾脏释放更高比例的肾素：肾素原。为检测转化酶活性增强情况，我们使肾上腺切除的（高转化酶）大鼠与肾切除的（低转化酶）大鼠交叉循环，并观察到它们共享血液中肾素原迅速下降，肾素增加。在体外混合它们的血液（无交叉循环）后也观察到这种情况，表明肾脏转化酶活性存在于血液中，而非仅存在于肾脏。对先前已肾上腺切除的大鼠进行急性肾切除，在15分钟内肾素降低而肾素原升高，提示肾脏来源的转化酶迅速丧失。这些结果不能归因于肾素底物浓度的变化。新的肾素（来自激活的肾外肾素原）被一种对正常大鼠血浆肾素有效的单克隆抗体阻断。它还产生免疫反应性血管紧张素I，表明与肾脏肾素在免疫和生物学上具有一致性。正常对照大鼠的血液在体内或体外均未表现出转化酶活性。这些数据表明肾外肾素原存在分泌（内分泌）来源，其受肾切除刺激，以及存在一种肾脏肾素原转化酶机制，该机制被肾切除消除并受肾上腺切除刺激。因此，在高肾素状态下，活性肾素可能通过循环肾素原（肾性和肾外性）的激活以及肾脏直接释放而产生。
