title: [Renin and aldosterone secretion under converting enzyme inhibition].
abstract: 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.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004285:Dogs; D005665:Furosemide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007552:Isotonic Solutions; D009638:Norepinephrine / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D011454:Prostaglandins A / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D012083:Renin / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007552:Isotonic Solutions; D011454:Prostaglandins A; D011458:Prostaglandins E; D000804:Angiotensin II; D012965:Sodium Chloride; D000450:Aldosterone; D005665:Furosemide; D011392:Proline; D002216:Captopril; D012083:Renin; D009638:Norepinephrine; D007213:Indomethacin