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Yeni Tanı Konmuş ve Tedavi Edilmemiş İzole Kan Basıncı Yüksekliği Olan Hastalarda Oksidatif DNA Hasarı: Olmesartanın Akut Etkisi

Oxidative Dna Damage in Newly Diagnosed and Untreated Patients with Isolated High Blood Pressure: The Acute Effect of Olmesartan

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DOI: 
DOI 10.5262/tndt.2012.1001.10
Abstract (2. Language): 
ObjectIves: Oxidative stress (OS) is the most important common pathway in the pathogenesis of endothelial and vascular damage related with the cardiovascular risk factors. Reactive oxygen species damage the macromolecules and DNA. 8-OHdG (8-hydroxy-2’-deoxyguanosine) is the reliable marker for oxidative DNA damage (ODD). To date, little is known about the presence of OS or ODD in patients with newly diagnosed and untreated primary hypertension (PHT), and the effects of antihypertensives on the ODD. The aims of the study was 1) to determine the oxidative DNA damage and to compare with normotensive healthy persons, 2) to determine the factors related with 8-OHdG level, and 3) to investigate the acute effect of olmesartan on 8-OHdG levels, in patients with newly diagnosed untreated PHT. MATE RIAL and MethodS: We enrolled 49 newly diagnosed, never treated, mild to moderate hypertensive patients with no additional cardiovascular or OS risk factors, and age and sex-matched 20 normotensive healthy persons. At the beginning of the study; biochemical tests, glomerular filtration rate measurement, and urinalysis were performed. Echocardiography was performed. 8-OHdG levels were obtained in all subjects. Olmesartan at a dose of 20 or 40 mg/day was administered for 4 weeks. All measurements were repeated after the treatment period. Res ults: Baseline mean levels of 8-OHdG (6.1±1.0 ng/ml) in patients were significantly higher than the control group (3.8±0.7 ng/ml) (p<0.001). Treatment with olmesartan significantly reduced the 8-OHdG levels independent of the blood pressure lowering effect. Mean levels of 8-OHdG after treatment were higher than the controls (4.6±0.9 ng/ml) (p<0.01). There was no correlation between 8-OHdG levels and demographic and laboratory values. ConclusI on: ODD is higher in patients with newly diagnosed untreated PHT than normotensive persons, and olmesartan seems to be improve ODD.
Abstract (Original Language): 
AMAÇ: Kardiyovasküler risk faktörlerinin damarsal hasarlanmada kullandıkları en önemli ortak yolak oksidatif strestir (OS). OS’ye bağlı reaktif oksijen türleri, büyük moleküllerde (lipid, protein vb.) ve DNA’da hasarlanmaya yol açar. 8-OHdG (8-hidroksi-2’-deoksiguanosin) oksidatif DNA hasarını (ODH) gösteren oldukça önemli bir moleküldür. Bugün, yeni tanı almış tedavisiz hipertansif hastalarda OS’ye bağlı ODH bulunup bulunmadığı ve antihipertansiflerin bu tabloya etkileri ile ilgili çalışma sayısı oldukça azdır. Çalışmanın amaçları, yeni tanı almış, tedavi edilmemiş ve OS açısından ek riski bulunmayan birincil hipertansiflerde; 1) ODH bulunup bulunmadığını belirlemek ve kan basıncı normal olanlarla karşılaştırmak, 2) 8-OHdG düzeyi ile ilişkili faktörleri belirlemek 3) olmesartanın 8-OHdG düzeyi üzerindeki akut etkisini araştırmaktı. GEREÇ ve YÖNTEMLER: Çalışmaya; yeni tanı almış, tedavi edilmemiş, OS açısından kan basıncı yüksekliği dışında OS risk faktörü bulundurmayan hafif-orta hipertansif 49 hasta ile, yaş ve cinsiyet uyumu sağlanmış, KB normal olan, OS açısından risk faktörü bulunmayan 20 sağlıklı birey alındı. Çalışma başlangıcında; biyokimyasal çalışmalar, glomerüler filtrasyon hızı, idrar testleri, ekokardiyografi ve serum 8-OHdG düzeyleri ölçümü yapıldı. Hastalara 4 haftalık 20 mg olmesartan tekli tedavisi verildi. Tedavi sonrası ölçümler yinelendi. Bulgular : Hastalarda ortalama serum 8-OHdG düzeyi (6,1±1,0 ng/ml) kontrol grubundan (3,8±0,7 ng/ml) anlamlı derecede yüksekti (p<0,001). Olmesartan tedavisi sonrası 8-OHdG düzeyi anlamlı olarak düştü (4,6±0,9 ng/ml) (p<0,01), ancak kontrol grubundan yine de yüksek düzeyde idi (p<0,01). Hastalarda 8-OHdG düzeyi ile ilintili bir faktör saptanmadı. Sonuç: Tedavi almayan yeni tanı konmuş ve hiçbir ek OS risk faktörü bulunmayan birincil hipertansiflerde ODH vardır. Olmesartan bu sorun üzerinde kan basıncına olan etkisinden bağımsız olarak olumlu etki göstermiştir.
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