Endothelin-converting enzyme inhibition ameliorates angiotensin II-induced cardiac damage
| Autor: | Bernd-Michael Löffler, Denise Blum-Kaelin, Hermann Haller, Joon-Keun Park, Henrietta Dehmlow, Bernhard Pilz, Alexander Mullally, Stefan Masur, Anette Fiebeler, Friedrich C. Luft, Dominik N. Müller, Johannes Aebi, Ralf Dechend |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Heart Diseases Heart Ventricles Angiotensinogen Endothelin-Converting Enzymes Kidney Muscle hypertrophy Animals Genetically Modified Rats Sprague-Dawley Oral administration Internal medicine Renin–angiotensin system Renin Internal Medicine medicine Animals Aspartic Acid Endopeptidases Humans Prodrugs RNA Messenger Enzyme Inhibitors Aorta Endothelin-1 business.industry Angiotensin II Metalloendopeptidases medicine.disease Immunohistochemistry Extracellular Matrix Fibronectins Rats Disease Models Animal Endocrinology medicine.anatomical_structure Blood pressure Echocardiography Heart failure Fibroblast Growth Factor 2 business Endothelin receptor |
| Zdroj: | Hypertension (Dallas, Tex. : 1979). 40(6) |
| ISSN: | 1524-4563 |
| Popis: | We tested the hypothesis that endothelin-converting enzyme (ECE) inhibition ameliorates end-organ damage in rats harboring both human renin and human angiotensinogen genes (dTGR). Hypertension develops in the animals, and they die by age 7 weeks of heart and kidney failure. Three groups were studied: dTGR (n=12) receiving vehicle, dTGR receiving ECE inhibitor (RO0687629; 30 mg/kg by gavage; n=10), and Sprague-Dawley control rats (SD; n=10) receiving vehicle, all after week 4, with euthanasia at week 7. Systolic blood pressure was not reduced by ECE inhibitor compared with dTGR (205±6 versus 206±6 mm Hg at week 7, respectively). In contrast, ECE inhibitor treatment significantly reduced mortality rate to 20% (2 of 10), whereas untreated dTGR had a 52% mortality rate (7 of 12). ECE inhibitor treatment ameliorated cardiac damage and reduced left ventricular ECE activity below SD levels. Echocardiography at week 7 showed reduced cardiac hypertrophy (4.8±0.2 versus 5.7±0.2 mg/g, P P P |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|