Acute kidney injury in the rat causes cardiac remodelling and increases angiotensin-converting enzyme 2 expression
| Autor: | L, Burchill, E, Velkoska, R G, Dean, R A, Lew, A I, Smith, V, Levidiotis, L M, Burrell |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Ventricular Remodeling
Reverse Transcriptase Polymerase Chain Reaction Myocardium Body Weight Drinking Angiotensin-Converting Enzyme Inhibitors Blood Pressure Acute Kidney Injury Peptidyl-Dipeptidase A Kidney Function Tests Nephrectomy Gene Expression Regulation Enzymologic Rats Proteinuria Urodynamics Heart Rate Heart Function Tests Animals Autoradiography Angiotensin-Converting Enzyme 2 Collagen RNA Messenger Fluorescent Dyes |
| Zdroj: | Experimental physiology. 93(5) |
| ISSN: | 0958-0670 |
| Popis: | Patients with kidney failure are at high risk of a cardiac death and frequently develop left ventricular hypertrophy (LVH). The mechanisms involved in the cardiac structural changes that occur in kidney failure are yet to be fully delineated. Angiotensin-converting enzyme (ACE) 2 is a newly described enzyme that is expressed in the heart and plays an important role in cardiac function. This study assessed whether ACE2 plays a role in the cardiac remodelling that occurs in experimental acute kidney injury (AKI). Sprague-Dawley rats had sham (control) or subtotal nephrectomy surgery (STNx). Control rats received vehicle (n = 10), and STNx rats received the ACE inhibitor (ACEi) ramipril, 1 mg kg(-1) day(-1) (n = 15) or vehicle (n = 13) orally for 10 days after surgery. Rats with AKI had polyuria (P0.001), proteinuria (P0.001) and hypertension (P0.001). Cardiac structural changes were present and characterized by LVH (P0.001), fibrosis (P0.001) and increased cardiac brain natriuretic peptide (BNP) mRNA (P0.01). These changes occurred in association with a significant increase in cardiac ACE2 gene expression (P0.01) and ACE2 activity (P0.05). Ramipril decreased blood pressure (P0.001), LVH (P0.001), fibrosis (P0.01) and BNP mRNA (P0.01). These changes occurred in association with inhibition of cardiac ACE (P0.05) and a reduction in cardiac ACE2 activity (P0.01). These data suggest that AKI, even at 10 days, promotes cardiac injury that is characterized by hypertrophy, fibrosis and increased cardiac ACE2. Angiotensin-converting enzyme 2, by promoting the production of the antifibrotic peptide angiotensin(1-7), may have a cardioprotective role in AKI, particularly since amelioration of adverse cardiac effects with ACE inhibition was associated with normalization of cardiac ACE2 activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text