Effects of long-term administration of octreotide on sodium retention and atrial natriuretic peptide in carbon tetrachloride-induced cirrhotic rats

Background/Aims: To realize the roles of peripheral vasolidation and atrial natriuretic peptide in the formation of cirrhotic ascites, the effects of long-term administration of octreotide on carbon tetrachloride-induced cirrhotic rats were evaluated. Methods: Urine sodium excretion, hemodynamics, plasma atrial natriuretic peptide levels, renin activities and aldosterone concentrations were compared between cirrhotic and control rats (protocol 1); and between octreotide- (65 μg/kg, twice daily for 10 days, subcutaneously) and placebo-treated (% dextrose) cirrhotic rats (protocol 2). In an in vitro experiment, right atrial tissue of cirrhotic rats was incubated with different concentrations of octreotide to evaluate the release of atrial natriuretic peptide (protocol 3). Results: Cirrhotic rats had significantly lower urine sodium excretion and systemic vascular resistance, and significantly higher plasma atrial natriuretic peptide levels, renin activities and aldosterone concentrations than control rats. Compared with placebo-treated cirrhosis rats, octreotide caused increased urine sodium excretion (–10±4% vs. 13±8% from baseline values, p<0.05) and systemic vascular resistance (2.6±0.1 vs. 3.3±0.3 mmHg•min•100 g•ml−1, p<0.05); and decreased plasma atrial natripretic peptide-levels (166.7±24.8 vs 234.±19.2 pg/ ml, p<0.05), renin activities (2.45±0.49 vs. 4.36±0.53 ng•ml−1•h−1, p<0.01) and aldosterone concentrations (290.2±40.0 vs. 483.3±82.6 pg/ml, p<0.05). In the in vitro experiment, right atrial release of atrial natriuretic peptide of cirrhotic rats was not significantly changed when incubated with different concentrations of octreotide. Conclusions: Octreotide ameliorates renal sodium retention and suppresses plasma levels of atrial natriuretic peptide of ascitic cirrhotic rats with a novel mechanism via, at least partly, the modification of peripheral vasucal resistance.