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ACE Inhibitörlerini n ve Aldosteron Reseptör Blokerlerinin Fibrinolitik Sistem Üzerindeki Etkileriyle ilgili Dinamik Karşılaştırmalı Bir Çalışma

A Dynamic Comparative Study Concerning the Effects of ACE Inhibitors and Aldosterone Receptor Blockers on Fibrinolytic System

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Abstract (2. Language): 
Backround: The renin-angiotensin-aldosterone system plays a central role in fibrinolysis. Activation of the RAAS stimulates the expression of plasminogen activator inhibitor (PAI-1), which can be directly implicated in the pathophysiology of thromboembolic events. Our primary aims were, 1) to measure the effect of acute RAAS activation on plasma levels of PAI-1, and 2) to measure the inhibitory effect of an ACE inhibitor alone, versus a combination of an ACE inhibitor and al-dosterone blocker on the usual increase in PAI-1 usually observed. Methods: In the current prospective in vivo study, RAAS was activated by means of phlebotomy, an effective, physiologic means of RAAS activation. Seventeen voluntary pre-hypertensive but otherwi¬se healthy blood donors were included in this study. Renin and PAI-1 levels were measured before and after initial phlebotomy. At the time of the second phlebotomy, 12/17 donors were randomly assigned to receive enalapril (5 mg) or the combination of enalapril (5 mg) plus spironolactone (25 mg), beginning three days prior to phlebotomy and 5 were assigned as controls who received no medications. Results: Plasma renin and PAI levels were significantly incre¬ased following initial phlebotomy. At the time of the second phle¬botomy, plasma PAI-1 activity was reduced significantly as compared to the initial phlebotomy, but it did not return to baseline levels. The observed mean reduction in PAI-1 level was greater for the subjects receiving both ACE and aldosterone inhibition. Conclusion: Enalapril and enalapril plus spironolactone effici¬ently reduce PAI-1 levels, but the reductions are more pronounced with the combined regimen. However, neither treatment appears sufficient to return PAI-1 activity to baseline levels.
Abstract (Original Language): 
Giriş: Renin-anjiyotensin-aldosteron sistemi (RAAS) fibrinolitik sistemde merkezi rol oynar. RAAS aktivasyonu tromboembolik olayların patofizyolojisinde direkt olarak yer alan plazminojen akti-vatör inhibitörünün (PAI-1) ekspresyonunu stimüle eder. Bu çalışmadaki primer amaçlarımız, 1) akut RAAS aktivasyonunun plazma PAI-1 düzeylerine olan etkisini ölçmek ve 2) yalnız başına ACE inhi-bitörü ve ACE inhibitörü ile kombine spironolaktonun PAI-1 düzeyleri üzerine etkilerini karşılaştırmaktı. Yöntem: Bu prospektif ve in vivo çalışmada RAAS efektif ve fizyolojik bir yol olan flebotomi ile aktive edildi. On yedi prehipertan-sif durum haricinde başka hastalığı bulunmayan gönüllü kan do-nörleri çalışmaya dahil edildi. Renin ve PAI-1 seviyeleri flebotomi öncesi ve sonrasında ölçüldü. İkinci flebotomi esnasında 17 donör-den 12'si, 6'sı enalapril (5 mg) ve diğer altısı enalapril+spironolak-ton (25 mg) almak üzere iki gruba ayrıldı; 5 donör ise kontrol grubu olarak seçildi. Bulgular: Plasma renin ve PAI-1 seviyeleri başlangıç flebotomi-sini takiben anlamlı olarak arttı. İkinci flebotomi esnasında, birincisine kıyasla plasma PAI-1 aktivitesi anlamlı olarak düştü; ancak bu düşüşün bazal seviyeye ulaşmadığı görüldü. PAI-1 seviyelerindeki ortalama düşüşün kombine medikasyon alan grupta daha fazla ol¬duğu gözlendi. Sonuç: Enalapril ve enalapril ile kombine spironolakton kullanımı PAI-1 seviyelerinde anlamlı düşüşe yol açmaktadır. Ancak bu düşüş kombine rejimle daha belirgin ortaya çıkmaktadır. Ne var ki, iki rejimde de PAI-1 aktivitesi bazal seviyelere düşmemektedir.
FULL TEXT (PDF): 
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