Hemodynamic effects of 8-day DL-028 and octreotide administration in rats with portal hypertension

Background: DL-028 (chemical name: 3-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]-2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one (27b)) is a synthetic alpha(1)-adrenoceptor antagonist. The present study was undertaken to investigate the hemodynamic effects of chronic DL-028 administration, alone or in combination with octreotide, in rats with portal hypertension. Methods: Portal hypertension was induced by partial portal-vein ligation. Portal-hypertensive rats were allocated to one of the four groups: vehicle group (saline, 0.5 ml/12 h), octreotide group (30 mu g/kg/12 h), DL-028 group (0.4 mg/kg/12 h), and octreotide (30 mg/kg/12 h) plus DL-028 (0.4 mg/kg/12 h) group, with eight rats in each group. DL-028 or saline was administered by gavage and octreotide by subcutaneous injection. Drugs were given immediately after ligation and for 8 consecutive days thereafter. Systemic and splanchnic hemodynamic variables were measured thereafter. Results: Portal-vein-ligated rats showed a typical hyperdynamic state as compared with sham-operated rats. The portal venous pressure, portal tributary blood flow, and cardiac index were significantly reduced by treatment with octreotide, DL-028, or octreotide plus DL-028 in portal-hypertensive rats. Hyperdynamic variables of systemic, renal, hepatocollateral, and portal territory vascular resistances and renal and hepatic arterial blood flow were ameliorated by treatment with octreotide or octreotide plus DL-028 in portal-hypertensive rats. Octreotide plus DL-028 treatment exerted better hemodynamic effects on the cardiac index but worse effects on systemic and hepatocollateral vascular resistance than octreotide treatment alone. Conclusion: Although either DL-028 or octreotide ameliorated portal hypertension and splanchnic hyperemia in portal-hypertensive rats, octreotide treatment exerted more beneficial hemodynamic effects than DL-028 treatment. The combination of octreotide and DL-028 conferred no better hemodynamic benefits than octreotide alone, except on the cardiac index.