Abstract
The formation of neointimal lesions and reocclusion of arteries are serious complications, that occur after percutaneous transluminal angioplasty. Proliferation of vascular smooth muscle cells (SMC) and enhancement of connective tissue synthesis are the major events in neointima formation. Angiotensin II not only regulates blood pressure but moreover induces SMC proliferation, and in cell cultures angiotensin II promotes hypertrophy and protein synthesis. In a balloon injury model it was tested whether or not antihypertensive agents which affect angiotensin II inhibit neointimal growth in carotid arteries. The angiotensin converting enzyme inhibitor Enalapril and the non peptide angiotensin II receptor antagonist Losartan were given orally to rats via drinking water at doses of about 15 mg/kg body weight/day. Losartan was also given at a low dose of 1.6 mg/kg/d. The animals received the drugs for one week before and for two weeks after experimental injury. Each group was represented by 9 to 12 animals. Cross sections from the middle third of the carotids were analysed with the aid of a videomorphometry system. The results show that at doses of 15 mg/kg/d Enalapril reduces neointimal growth for about 14.5 % (p < 0.025) and Losartan for about 31 % (p < 0.001). Even 1.6 mg Losartan/kg/d effectively reduced the sizes of neointimal lesions (32 %, p < 0.001). In conclusion, Losartan is obviously a very potent agent of a new class of angiotensin II receptor antagonists with both antihypertensive and antiarteriosclerotic qualities.
Zusammenfassung
Die Bildung neointimaler Läsionen istsehrwahrscheinlich der Mechanismus, der bei Restenosierungen nach koronarangiographischen Eingriffen auftritt [1]. Wesentliche Faktoren des damit verbundenen neointimalen Wachstums sind die Proliferation glatter Gefäßmuskelzellen (SMC) und die vermehrte Synthese von Bindegewebe. Die Proliferation von SMCs wird durch Angiotensin II, dessen Funktion als blutdruckregulierende Substanz bereits gut bekannt ist, angeregt [5]. In Zellkulturen wurde nachgewiesen, daß Angiotensin II zur Hypertrophierung und zu verstärkter Proteinsynthese von SMCs führt [2, 6]. Angiotensin II entsteht aus Angiotensin I mit Hilfe des Angiotensinkonversionsenzyms ACE. Über Rezeptoren in der Gefäßwand reguliert Angiotensin II offensichtlich nicht nur den Blutdruck, sondern direkt oder indirekt, z. B. über das intrazelluläre Kalzium, Zeltvermehrung und Bindegewebesynthese [3, 7, 12]. Aus diesem Grunde sind Hemmer von Angiotensin II möglicherweise von zusätzlichem therapeutischem Nutzen bei der Unterdrückung von Restenosen. Im vorliegenden Fall wurden in ballonisierten Ratten die Wirkungen von zwei Substanzen geprüft und verglichen, die auf verschiedene Weise Angiotensin II-Aktivitäten hemmen. Der ACE-Inhibitor Enalapril hemmt das Angiotensin-Konversionsenzym. Der nichtpeptidische Angiotensin II-Rezeptorantagonist Losartan, der auch unter den Bezeichnungen DuP753, EXP115 und MK954 bekannt ist, bindet an Angiotensin II- Rezeptoren und verhindert die Bindung von Angiotensin II [11].
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© 1993 Springer Fachmedien Wiesbaden
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Völker, W. et al. (1993). The ACE inhibitor Enalapril and the angiotensin II receptor antagonist Losartan inhibit neointimal thickening in balloon-injured rat carotid arteries. In: Heinle, H., Schulte, H., Schaefer, H.E. (eds) Diätetik und Arteriosklerose. Vieweg+Teubner Verlag, Wiesbaden. https://doi.org/10.1007/978-3-663-01942-8_67
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DOI: https://doi.org/10.1007/978-3-663-01942-8_67
Publisher Name: Vieweg+Teubner Verlag, Wiesbaden
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