Received December 19, 2007
Revised January 4, 2008
Accepted after revision January 4, 2008
Differential regulation of renal ACE2 and ACE during ACE inhibition and dietary sodium restriction in healthy rats
Inge Hamming 1,
Harry van Goor 1*,
Anthony Turner 2,
Chris Rushworth 2,
Annie Michaud 3,
Pierre Corvol 3,
Gerjan Navis 1
1 University Medical Center Groningen
2 University of Leeds
3 College de France
* To whom correspondence should be addressed. E-mail: h.van.goor{at}path.umcg.nl.
 |
Abstract |
|---|
Abstract
ACE2 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 the regulation vary among each other. To enhance our understanding on the regulation of renal ACE2 and ACE, we investigated renal ACE and ACE2 expression during conditions of physiological (low sodium diet) and pharmacological (ACE inhibition) changes in RAAS activity.
Healthy rats were treated with vehicle or lisinopril either with a control or a low sodium diet and renal ACE2, ACE and plasma angiotensins were studied.
During vehicle, 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 ACEi, low sodium reduced both ACE and ACE2 mRNA without affecting ACE2 activity or further reducing ACE activity. Renal Neprelysin activity measurements 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) by the ACE inhibitor lisinopril, especially during a low sodium intake.
In conclusion, modulation of the RAAS, by low sodium intake or ACE inhibition, does not affect renal ACE2 despite major variations in renal ACE. Thus, ACE and ACE2 are differentially regulated by low sodium and ACE inhibition. Therefore, we propose that renal ACE and ACE2 are differentially regulated by low sodium and ACE inhibition. Whether this also applies to renal disease conditions, and accordingly the renoprotective effects of ACE inhibition should be investigated in further studies.
Key Words:
Angiotensin, Kidney, Sodium
