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, and systemic circulatory effects F-180, a new long-acting analog of vasopressin (VP) with selective effect on the vascular (V-1) receptor, both in normal rats and in portal-hypertensive animals, In preliminary vasopressor 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 times 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-hypertensive rats with partial portal vein ligation (PPVL), the vasopressor 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%), whereas TP at 8.10 nmol x kg(-1) was required to achieve comparable splanchnic effects; however, this dose caused a significantly greater increase 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 caused a significantly greater elevation in systemic vascular resistance (SVR) and MAP, and more pronounced reduction in cardiac index (P < .05).