Nakamura K
Nihon Naibunpi Gakkai Zasshi. 1983 Aug 20;59(8):1099-116. doi: 10.1507/endocrine1927.59.8_1099.
The converting enzyme inhibitor (CEI) is known to inhibit the conversion of angiotensin I to angiotensin II. In order to analyse the regulatory mechanisms involved in aldosterone secretion independent of renin-angiotensin system, one of the CEIs, SQ 14,225 was infused to the dogs in association with several pharmacological agents. To the mongrel dogs under pentobarbital anesthesia, SQ 14,225 was administered intravenously as a bolus injection (0.5 mg/kg), followed by two hour infusion (0.5 mg/kg/hr). The effects of several pharmacological agents on plasma renin activity (PRA) and aldosterone concentration (PA) were examined in the condition in which endogenous angiotensin II production was blocked by CEI. PRA was increased significantly from the basal level (6.4 +/- 1.2; mean +/- SEM) to 14.1 +/- 2.6 ng/ml/hr 60 min after the administration of SQ 14,225. PA, on the other hand, was decreased from 12.2 +/- 3.6 to 7.6 +/- 2.2 ng/dl. The CEI-induced increase in PRA was completely blocked by infusion of angiotensin II (40 ng/kg/min), physiological saline (0.25 approximately 0.44 ml/kg/min), pretreatment of propranolol (0.5 mg/kg) or norepinephrine (200 ng/kg/min). Both pindolol and indomethacin had no significant effect on the CEI-induced increase in PRA. Increase in PRA was also observed by the infusion of furosemide, prostaglandin 1 or E1. PA was increased by KCl infusion (1.0 mEq/kg/hr), but was not affected significantly by the administration of furosemide, pindolol, prostaglandin A1 or E1, during the SQ 14,225 infusion. An elevation of PRA observed under the converting enzyme inhibition, was considered to be due to decreased feedback inhibition as a result of reduction of angiotensin II formation. It was suggested from the present results, that the CEI-induced increase in PRA might be mediated by beta-receptor and baroreceptor in addition to the direct negative feedback by angiotensin II. The present data also suggested that both furosemide and prostaglandins stimulated aldosterone secretion via the renin-angiotensin system, rather than by acting directly on the adrenal cortex.
已知转换酶抑制剂（CEI）可抑制血管紧张素I向血管紧张素II的转换。为了分析独立于肾素-血管紧张素系统的醛固酮分泌调节机制，将一种CEI，即SQ 14,225与几种药理剂联合注入犬体内。对戊巴比妥麻醉下的杂种犬，静脉推注SQ 14,225（0.5mg/kg），随后两小时输注（0.5mg/kg/小时）。在CEI阻断内源性血管紧张素II产生的情况下，研究了几种药理剂对血浆肾素活性（PRA）和醛固酮浓度（PA）的影响。注射SQ 14,225后60分钟，PRA从基础水平（6.4±1.2；平均值±标准误）显著升高至14.1±2.6ng/ml/小时。另一方面，PA从12.2±3.6降至7.6±2.2ng/dl。注入血管紧张素II（40ng/kg/分钟）、生理盐水（0.25约0.44ml/kg/分钟）、普萘洛尔预处理（0.5mg/kg）或去甲肾上腺素（200ng/kg/分钟）可完全阻断CEI诱导的PRA升高。吲哚洛尔和吲哚美辛对CEI诱导的PRA升高均无显著影响。静脉输注速尿、前列腺素1或E1也观察到PRA升高。在输注SQ 14,225期间，静脉输注氯化钾（1.0mEq/kg/小时）可使PA升高，但速尿、吲哚洛尔、前列腺素A1或E1的给药对其无显著影响。在转换酶抑制作用下观察到的PRA升高，被认为是由于血管紧张素II生成减少导致反馈抑制降低所致。从目前的结果来看，提示CEI诱导的PRA升高除了血管紧张素II的直接负反馈外，可能还由β受体和压力感受器介导。目前的数据还表明，速尿和前列腺素均通过肾素-血管紧张素系统刺激醛固酮分泌，而不是直接作用于肾上腺皮质。
