Factors regulating renal angiotensin-converting enzyme activity in the rat.

Abstract

Changes in angiotensin-converting enzyme (ACE) activity appear to be important in mediating the natriuresis which ensues after administration of an oral or gastric sodium load. In this study, we sought to determine the time course of the changes in ACE activity in the kidney which occur after sodium ingestion. In addition, we sought to investigate mechanisms which might underlie these changes. Angiotensin-converting enzyme activity was measured by generation of histidyl-leucine in homogenates of kidneys harvested at varying time-points after gastric sodium administration. The effects of intravenous sodium loading, solution osmolality and of changes in renal nerve activity were also investigated. Intragastric instillation of both the sodium-containing solution and its iso-osmotic urea control solution resulted in significant increases in renal ACE activity (NaCl: P < 0.0005; Urea: P < 0.01). The increase in renal ACE activity after gastric sodium loading was more prolonged than after the urea control (P < 0.025, NaCl vs. urea at 90 min). This prolonged increase in renal ACE activity appeared to reflect a response to absorbed sodium as intravenous sodium administration caused a significant increase in renal ACE activity at 90 min (P < 0.0005). In contrast to these stimuli which increased renal ACE activity, renal denervation caused a significant decrease in ACE activity in the kidney (P < 0.05). We conclude that gastric sodium loading increases renal ACE activity. This effect appears to be due initially to a response to an increase in gastric lumenal osmolality and later to absorbed sodium. These changes in renal ACE activity are not mediated by a decrease in renal nerve activity.