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2003, Cilt 1, Sayı 3, Sayfa(lar) 109-117
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The Effects of Propranolol and Octreotide Treatments on Liver and Vascular Endothelium in Rats with Pre-Hepatic Portal Hypertension
Ahmet Var1, Yeşim Güvenç1, Ece Onur1, Kemal Özbilgin2, Gülşen Giray2, Özer İlkgül3, Zeki Arı1
1Celal Bayar Üniversitesi Tıp Fakültesi Biyokimya AD, Manisa
2Celal Bayar Üniversitesi Tıp Fakültesi Histoloji ve Embriyoloji AD, Manisa
3Celal Bayar Üniversitesi Tıp Fakültesi Genel Cerrahi AD, Manisa
Keywords: Portal hypertension, free radicals, endothelial dysfunction, octreotide, propranolol

Purpose: Portal hypertension (PHT) is a common clinical syndrome, characterized by a pathological increase in portal pressure and hemodynamic changes. It is known that the oxidative stress is a mediator in the pathogenesis of PHT. Beta-blockers (propranolol), somatostatin and analogs of longacting somastatin (octreotide) that all have an effect on the portal blood flow may be used for treatment. In this study it was aimed to investigate the effects of propranolol and octreotide that may be used for treatment of PHT to oxidative stress. For this purpose, myeloperoxidase (MPO), malondialdehyde (MDA), nitric oxide (NO) levels, and the inducible NOS (i-NOS), endothelial NOS (e-NOS) were evaluated by histochemical techniques.

Material and Methods: 58 male wistar rats weighed 200 to 240 gr were randomly selected and separated into four groups. Surgical operations were performed after an anesthesia with ketamine (50 mg/kg, IM). Groups were structured as: Sham (Group I), PHT (Group II), PHT + octreotide (Group III), PHT + propranolol (Group IV).

Induction of prehepatic portal hypertension was performed to Group II, III and IV for eight weeks. All rats were sacrificed by cervical dislocation and laporatomy was performed. MDA in tissue by TBARS method, MPO by the method explained by Wei et al spectrophotometrically, NO by Griess method, i-NOS and e-NOS by histochemical methods were evaluated in all groups.

Results: MDA, MPO and NO levels were significantly higher in group II (PHT) than Group I (Sham) (p=0.001, p=0.05, p=0.05, respectively). The MPO levels in group III (PHT and octreotide) were significantly higher than Group II (PHT) and Group IV (PHT+propranolol) (p<0.01, p<0.05, respectively). NO levels in group IV were significantly higher than in both Group II and III with portal hypertension (p<0.05). Mild e-NOS immunoreactivity was observed in hepatic endothelial cells in Group I, no similar activity was observed in parenchymal cells. However, in Group IV (PHT + propranolol) e-NOS immunoreactivity was higher than parenchymal cells. No i-NOS immunoreactivity was observed in two kinds of tissue in Group I (Sham). An increase of i-NOS immunoreactivity in parenchymal cells and perivasculer area was detected in Group II. It was observed that i-NOS immunoreactivity increased mildly in Group III and highly in Group IV.

Conclusions: It was seen that octreotide, one of the two different medicine used in the treatment of PHT, increased neutrophil activation via the effect of MPA and propranolol increased oxidative stress in PHT via NO. Applying propranolol increased levels of i-NOS more than e-NOS histochemically. Therefore these two drugs should be used cautiously in the treatment of portal hypertension due to these adverse-effects.


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