Antihypertensive Treatment Approaches and Oxidant-Antioxidant System Relationship in Hypertensive Type 2 Diabetic Patients

Öz

A relationship between endothelial dysfunction and oxidative stress has been shown in the pathogenesis of diabetes and/or hypertension. Antihypertensive drugs (angiotensin-converting enzyme inhibitors [ACEi], angiotensin II type 1 receptor blockers [ARB], and third-generation beta-blockers) can improve oxidative stress. This study evaluated the effects of losartan (ARB) treatment alone and combined with cilazapril (ACEi) or carvedilol on oxidative stress and antioxidants in hypertensive type 2 diabetic patients. Thirty of 56 patients completed the study. All patients received 50 mg losartan daily for 6 weeks, then were randomised into three groups for 6 weeks. In the first group, losartan was increased to 100 mg/day, and in the second and third groups, carvedilol or cilazapril was added to losartan 50 mg/day treatment, respectively. Apolipoprotein B malondialdehyde (basal and Δ-MDA), serum paraoxonase (PON) and arylesterase (AE), erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (Gpx) parameters were studied. The characteristics of the three groups were comparable (p>0.05). Blood pressure (BP) decreased significantly in all three groups before and after randomisation in the six-week periods. The largest BP decrease was seen in the ARB+ACEi group (systolic BP: 16.5±7.4 mmHg, diastolic BP: 10.5±2.8 mmHg), and the smallest decrease was seen in the high-dose ARB group (systolic BP: 9±6.1 mmHg, diastolic BP: 3±4.8 mmHg). Throughout the study, no significant changes were detected in basal and Δ-MDA levels and SOD, Gpx, PON and AE activities in inter- and intra-group comparisons. Our observations showed that different antihypertensive therapy approaches effectively lowered BP in hypertensive type 2 diabetics but did not affect oxidant and antioxidant systems in the short term.

Anahtar Kelimeler

• Type 2 diabetes mellitus
• Hypertension
• Antihypertensive agents
• Oxidative stress
• Antioxidants
• Losartan
• Cilazapril
• Carvedilol

Hipertansif Tip 2 Diyabetik Hastalarda Antihipertansif Tedavi Yaklaşımları ve Oksidan-Antioksidan Sistem İlişkisi

Öz

Diyabet ve/veya hipertansiyon patogenezinde endotel disfonksiyonu ile oksidatif stres arasında ilişki olduğu bildirilmiştir. Antihipertansif ilaçlar (anjiyotensin dönüştürücü enzim inhibitörleri [ACEi], anjiyotensin II tip 1 reseptör blokerleri [ARB] ve üçüncü nesil beta blokerler) oksidatif stresi iyileştirebilirler. Bu çalışmada losartan (ARB) tedavisinin tek başına ve silazapril (ACEi) veya karvedilol ile birlikte kullanımının, hipertansif tip 2 diyabetik hastalarda oksidatif stres ve antioksidanlar üzerindeki etkilerini değerlendirildi. Elli altı hastadan 30'u çalışmayı tamamladı. Tüm hastalar 6 hafta boyunca günlük 50 mg losartan aldı, sonra altı hafta için 3 gruba randomize edildiler. İlk grupta losartan 100 mg/gün'e çıkıldı, ikinci ve üçüncü gruplarda losartan 50 mg/gün tedavisine sırasıyla karvedilol veya silazapril eklendi. Apo B-içeren lipoproteinlerin malondialdehit (bazal ve Δ-MDA), paraoksonaz (PON), arilesteraz (AE), eritrosit süperoksit dismutaz (SOD) ve glutatyon peroksidaz (Gpx) parametreleri çalışıldı. Üç grubun karakteristikleri karşılaştırılabilirdi (p>0.05). Her üç grupta da randomizasyon öncesi ve sonrası altışar haftalık dönemlerde kan basınçları (KB) anlamlı şekilde azaldı (p<0.05). En fazla KB düşüşü ARB+ACEi grubunda (sistolik KB: 16.5±7.4 mmHg, diyastolik KB: 10.5±2.8 mmHg) ve en küçük düşüş yüksek doz ARB grubunda (sistolik KB: 9±6.1 mmHg, diyastolik KB: 3±4.8 mmHg) görüldü. Çalışma boyunca gruplar arası ve grup içi karşılaştırmalarda bazal ve Δ-MDA, SOD, Gpx, PON ve AE aktivitelerinde anlamlı bir değişiklik saptanmadı. Gözlemlerimiz hipertansif tip 2 diyabetiklerde farklı antihipertansif terapi yaklaşımlarının KB’nı düşürmede etkili olduklarını fakat kısa dönemde oksidan ve antioksidan sistemleri etkilemediğini göstermiştir.

Anahtar Kelimeler

• Tip 2 diabetes mellitus
• Hipertansiyon
• Antihipertansif ilaçlar
• Oksidatif stres
• Antioksidanlar
• Losartan
• Silazapril
• Karvedilol

Kaynakça

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