Nur Banu BAL, Orhan Mecit ULUDAĞ, Emine DEMİREL YILMAZ

Nefrektomi yapılmadan oluşturulan DOCA-tuz modelinin kan basıncı, kalp ve böbrek işlevlerine etkisi

Amaç: Hipertansiyon, gelişiminde pek çok faktörün rol oynadığı, en yaygın kardiyovasküler hastalıktır. Deoksikortikosteron asetat (DOCA)-tuz modeli, esansiyel hipertansiyonun patogenezinin araştırılmasında oldukça sık kullanılan bir deneysel modeldir. Bu model, insanlardaki esansiyel hipertansiyonu başarılı bir şekilde taklit edebilmektedir. Ancak tek taraflı nefrektomi uygulaması ile hızlı ve şiddetli kan basıncı artışı oluşturması, çoğu hipertansif hastadaki klinik durumu tam olarak yansıtmamaktadır. Bu çalışmada, nefrektomi yapılmadan uzun süre DOCA-tuz uygulamasının sıçanların kan basıncı, vücut ağırlığı, kalp ve böbrek işlevleri üzerindeki etkileri incelenmiştir. Yöntem: Çalışmada erkek Wistar Albino sıçanlar (8 haftalık) kullanılmıştır. DOCA-tuz hipertansiyon modelini oluşturmak için 12 hafta boyunca sıçanlara haftada iki kez DOCA enjeksiyonu (20 mg/kg, s.c.) yapılmış ve içme sularına tuz (% 1 NaCl ve %0,2 KCl) eklenmiştir. Sıçanların sistolik kan basınçları ve vücut ağırlıkları her hafta ölçülmüştür. Deneyin sonunda anestezi altındaki sıçanlardan kan örnekleri alınarak santrifüjlenmiş ve plazma elde edilmiştir. Sıçanların sağ atriyum ve sol papiller kas dokuları izole edilmiş ve dokuların fenilefrin, izoprenalin ve asetilkolin uygulanmasına bağlı kasılma cevapları ile ritmik aktivitesi organ banyosunda kaydedilmiştir. Plazma örneklerinde kan üre azotu (BUN) ve kreatinin düzeyleri ölçülmüştür. Bulgular: Nefrektomi yapılmadan 12 hafta süreyle DOCA-tuz uygulaması, sıçanların kan basıncında anlamlı olarak yükselmeye neden olmuştur. Hipertansif sıçanlarda sağ atriyumun fenilefrinle uyarılan alfa adrenerjik reseptör aracılı kasılma cevapları artmış, izoprenalinle oluşturulan beta adrenerjik reseptör aracılı kasılma cevabı azalmış ve asetilkolin cevapları değişmemiştir. DOCA-tuz uygulaması sıçanların plazma BUN ve kreatinin düzeylerini yükseltmiştir. Sonuç: Elde edilen sonuçlar; nefrektomi yapılmadan 12 hafta boyunca DOCA-tuz uygulamasının, hipertansiyonla ilişkili kardiyak ve renal değişikliklere neden olduğunu ve noninvaziv hayvan modeli olarak hipertansiyon çalışmalarında kullanılabileceğini göstermektedir.

The effect of DOCA-salt model without nephrectomy on blood pressure, heart and kidney functions

Objective: Hypertension is one of the common cardiovascular diseases in which many factors play a role in its development. The deoxycorticosterone acetate (DOCA)-salt model is an experimental model that is widely used in the investigation of the pathogenesis of essential hypertension. Although this model can successfully mimic essential hypertension in humans, both the rate and magnitude of blood pressure increase with unilateral nephrectomy does not fully reflects the clinical situation in most hypertensive patients. In this study, it was investigated the effects of prolonged administration of DOCA-salt without nephrectomy on blood pressure, body weight, heart and kidney functions of rats. Methods: Male Wistar Albino rats (8-week-old) were used in the study. DOCA-salt hypertension model was induced by DOCA injection (20 mg/kg, s.c.) twice a week and and by adding salt (1% NaCl and 0.2% KCI) to drinking water for 12 weeks. Systolic blood pressures and body weights of all rats were measured weekly. At the end of the experiment, blood samples were taken from anesthetized rats, centrifuged, and plasma was collected. Right atrium and left papillary muscle tissues were isolated from rats. Isoprenaline, phenylephrine and acethylcholine-induced rhythmic activity and contractions of tissues were recorded in organ bath. Blood urea nitrogen (BUN) and creatinine levels were measured in plasma samples. Results: 12 weeks DOCA-salt administration without nephrectomy were significantly elevated systolic blood pressure of rats. The DOCA-salt application did not cause a decrease in the body weight of the rats. While the right atrium was not affeced to acethylcholine; the phenylephrine-induced alpha adrenergic receptor mediated contractile responses were increased and the isoprenaline-induced beta adrenergic receptor-mediated contractile responses were decreased in hypertensive rats. The DOCA-salt administration increased plasma BUN and creatinine levels of rats. Conclusion: These findings suggest that 12 weeks DOCA-salt administration without nephrectomy caused cardiac and renal changes associated with hypertension and could be used in hypertension studies as a noninvasive animal model.

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