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Einfluss des ACE-NEP-Inhibitors AVE 7688 und des ACE-Hemmers Ramipril auf die Mortalität von spontan hypertensiven Ratten unter besonderer Berücksichtigung der Gefäß-, Nieren- und Herzfunktion
| Content Provider | Semantic Scholar |
|---|---|
| Author | Afkham, Freni |
| Copyright Year | 2003 |
| Abstract | Hypertension is an important risk factor for manifestation and endpoints of cardiovascular diseases, such as stroke, myocardial infarction and congestive heart failure. Hypertension is usually preceeded by an endothelial dysfunction, which itself deteriorates through hypertension. The RAAS plays a crucial role in the development and progression of ED, hypertension, renal and cardiac failure. This fact has been successfully therapeutically explored through the use of ACE-inhibitors and AT1-receptor antagonists. However, so far the role of NEP in the context of cardiovascular diseases remains unclear. In this study the effects of chronic treatment of spontaneoulsy hypertensive rat (SHR) at the age of 15 months with Ramipril (ACE-inhibitor) and AVE 7688 (ACE-NEP-inhibitor) were investigated. Beside their effects on mortality, the effects on cardiac, renal and vascular function was analyzed. The main result is that both Ramipril and AVE 7688 affected positively the most relevant parameter for cardiac, renal and vascular function and decreased mortality. Both compounds improved albuminuria and Creatinine-Clearance in the kidney. They also improved the crucial markers for ED, such as production of NO, superoxide, PAI and aortic relaxation. AVE 7688 and Ramipril also improved cardiac markers for heart failure, such as pro-ANP and cardiac hypertrophy. The positive effects of these compounds on renal, vascular and cardiac function was also reflected in a decreased mortality, where the treated animals reached basically the life duration of normal animals. These results underline the potential of these compounds for the treatment of cardiovascular diseases. Another conclusion for the settings of this study is that the differences in efficacy between Ramipril and AVE 7688 is rather small. Both showed very similar effects on most of the investigated parameters. Nevertheless, there were several differences between the compounds which could be of potential benefit in specific pouplations. In the kidney, AVE 7688 decreased albuminuria significantly better than Ramipril. As this is a very important marker for the progression of nephropathy, the result could have implication for the treatment of this disease. AVE 7688 also increased significantly higher than Ramipril NO production while decreasing superoxide synthesis. Considering the importance of these second messengers for the development of endothelial dysfunction and subsequent atherosclerosis, this difference could also be a potential advantage of a AVE 7688 therapy. Although there were no significant differences between Ramipril and AVE 7688 on cardiac parameters, it should be noted that the tendency for a better antihypertrophic efficacy of AVE 7688 was observed. All results described here resulted in a dramatically decreased mortality in the treated animal groups. Again, AVE 7688 appeared to have a greater impact on mortality, but this result was also not significant. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://elib.tiho-hannover.de/servlets/MCRFileNodeServlet/etd_derivate_00002683/afkhamf_2003.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
