Differential regulation of renal angiotensin-converting enzyme (ACE) and ACE2 during ACE inhibition and dietary sodium restriction in healthy rats

Experimental Physiology
I HammingG J Navis

Abstract

Angiotensin-converting enzyme (ACE) 2 is thought to counterbalance ACE by breakdown of angiotensin (Ang) II and formation of Ang(1-7). Both enzymes are highly expressed in the kidney, but reports on their regulation differ. To enhance our understanding of the regulation of renal ACE and ACE2, we investigated renal ACE and ACE2 expression during conditions of physiological (low-sodium diet) and pharmacological changes (ACE inhibition) in activity of the renin-angiotensin-aldosterone system (RAAS). Healthy rats were treated with vehicle or lisinopril with either a control or a low-sodium diet, and renal ACE2, ACE and plasma angiotensins were studied. During vehicle treatment, low sodium reduced renal ACE mRNA and activity without affecting ACE2 mRNA or activity and plasma Ang(1-7) and Ang II balance. Lisinopril significantly reduced renal ACE activity without affecting renal ACE2 activity. During ACE inhibition, low sodium reduced both ACE and ACE2 mRNA without affecting ACE2 activity or further reducing ACE activity. Measurements of renal neprilysin activity revealed no significant differences between any of the treatment groups. Plasma Ang(1-7) and Ang II balance is positively shifted towards the beneficial vasopeptide Ang(1-7)...Continue Reading

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