Anjiotensin Dönüştürücü Enzim İnhibitörleri Ve Angiotensin Reseptör Blokörlerinin İnflamasyona Etkisi

Öz

Amaç: Renin Anjiotensin Sistemi(RAS) renal, kardiyovasküler, inflamatuvar ve adrenal fonksiyonlara etki eden önemli bir sistemdir. Bu sistemi enzim ve reseptör düzeyinde bloke eden ilaçlar, akut myokard infarktüsü, konjestif kalp yetmezliği, hipertansiyon, diyabetik nefropati-proteinüri tedavisinde yaygın olarak kullanılmaktadır. Bu çalışma, bu sistemi bloke eden ilaçların inflamasyon üzerindeki etkilerini ortaya koymayı amaçlamıştır. Gereç ve Yöntemler: Çalışmamızda üç farklı dozda uygulanan Anjiotensin dönüştürücü enzim inhibitörleri (kaptopril, enalapril, lizinopril) ve Anjiotensin reseptör (AT1) blokeri losartan’ın inflamasyonun akut fazına etkileri karragenin inflamasyon modelinde, kronik fazına etkileri ise koton pellet granüloma modelinde sıçanlarda test edildi. Bulgular: Karragenin modelinde, inflamasyonunun 2. saatinde kaptopril (100 mg/kg) önemsiz bir antiinflamatuvar etki yaparken, enalapril (20 mg/kg) ve lizinopril (50 mg/kg) %33.35 , ve %16.91 oranlarında proinflamatuvar etki yapmışlardır (p<0.05). Losartan(50 mg/kg) aynı saatte inflamasyonu % 43.69 oranında azaltmıştır, bu azalma kontrol ve diklofenak gruplarına oranla istatistiksel olarak anlamlı bulunmuştur (p<0.05). Koton pellet modelinde, kaptopril, enalapril, lizinopril, losartan, diklofenak (25 mg/kg) ve prednisolon’un (10 mg/kg) antiproliferatif etkileri sırasıyla % 35.78 , % 36.87, % 24.06, %30.19 % 58.36 ve % 55.11 olarak saptanmıştır ve bu sonuçlar kontrol grubuna oranla istatistiksel olarak anlamlıdır (p<0.05). Sonuç: ADE inhibitörleri akut pençe ödemi modelinde proinflamatuvar, kronik inflamasyon modelinde belirgin antiproliferatif etki sergilemiştir. Losartan, hem akut hem kronik modelde önemli derecede antiinflamatuvar etki göstermiştir. Losartan’ın bu etkisinde AT1 reseptörlerin rol oynadığı düşünülmektedir.

Anahtar Kelimeler

• kaptopril
• enalapril
• losartan
• pençe ödemi
• koton pellet
• inflamasyon

Effects Of Angiotensin-Converting Enzyme (Ace) İnhibitors And Angiotensin Receptor Blockers On Iflammatıon

Öz

Background: Renin-Angiotensin system is an important system which has affected on renal, cardiovascular, inflammatory and adrenal functions. Drugs blocking this system at enzyme and receptor levels are frequently used at therapies of acute myocardial infarction, congestive heart failure, hypertension, diabetic nephropathy - proteinuria. This study aimed to reveal the effects of drugs that block this system on inflammation. Method: In our study, the effects of three different doses of Angiotensin Converting Enzyme (ACE) inhibitors (captopril, enalapril, lisinopril) and angiotensin receptor (AT1) blocker losartan, were tested with carrageenan model on acute phase of inflammation and with cotton pellet granuloma model on chronic phase of inflammation in rats. Results: In carrageenan model, at the second hours of the inflammation, while captopril (100 mg/kg) showed insignificant antiinflammatory effect, enalapril (20 mg/kg) and lisinopril (50 mg/kg) presented proinflammatory effects at rates of 33.35 % and 16.91 % (p<0.05). At same hour, losartan, 50 mg/kg, decreased the inflammation at rate of 43.69 %, this result was significant statistically, compared to control and diclofenac groups (p<0.05). In the cotton pellet model, antiproliferative effects of captopril, enalapril, lisinopril, losartan, diclofenac (25 mg/kg) and prednisolone (10 mg/kg) were calculated at rates of 35.78 %, 36.87 %, 24.06 %, 30.19 %, 58.36 % and 55.11 %, respectively, and these results were significant statistically, compared to control group (p<0.05). Conclusion: ACE inhibitors presented the proinflammatory effects in carrageenan induced acute paw oedema model, significant antiproliferative effects in chronic inflammation models. Losartan, Angiotensin receptor blocker, showed significant antiinflammatory effects in both acute and chronic inflammation models. It was thought that AT1 receptors had played important role in these effects of losartan.

Anahtar Kelimeler

• captoril
• enalapril
• losartan
• paw edema
• cotton pellet
• inflammation

Kaynakça

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