EFFECTS OF F-180, A NEW SELECTIVE VASOCONSTRICTOR PEPTIDE, COMPARED WITH TERLIPRESSIN AND VASOPRESSIN ON SYSTEMIC AND SPLANCHNIC HEMODYNAMICS IN A RAT MODEL OF PORTAL-HYPERTENSION

The present study is aimed at characterizing the portal, splanchnic, a nd systemic circulatory effects F-180, a new long-acting analog of vas opressin (VP) with selective effect on the vascular (V-1) receptor, bo th in normal rats and in portal-hypertensive animals, In preliminary v asopressor tests, F-180 was 18 times more potent than terlipressin (TP ) (164 +/- 10 IU x mmol(-1) vs. 9.2 +/- 1.2 IU x mmol(-1)) and four ti mes less potent than arginine VP (614 +/- 25 IU x mmol(-1)). F-180 had negligible antidiuretic potency, resulting in vascular selectivity (V -1/V-2) of 858 compared with 1.0 for VP and 2.2 for TP. In portal-hype rtensive rats with partial portal vein ligation (PPVL), the vasopresso r effect of F-180 was 19 times that of TP on a molar basis (ED50 F-180 : 0.54 vs. TP: 10.02 nmol x kg(-1)). At low doses (0.405 nmol x kg(-1) ), F-180 significantly reduced portal pressure (PP) (-13.8% +/- 6.7%) and superior mesenteric artery blood flow (SMABF) (-25.6% +/- 4.5%), w hereas TP at 8.10 nmol x kg(-1) was required to achieve comparable spl anchnic effects; however, this dose caused a significantly greater inc rease in mean arterial pressure (MAP) than F-180 at 0.405 nmol x kg(-1 ) (28.2% +/- 2.7% vs, 8.9% +/- 2.7% at 20 minutes; P < .05). F-180 at 0.405 nmol x kg(-1) had effects on PP and SMABF similar to a 30-minute intravenous infusion of VP at 10 mU x kg(-1) in PPVL rats, but VP cau sed a significantly greater elevation in systemic vascular resistance (SVR) and MAP, and more pronounced reduction in cardiac index (P < .05 ).