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

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Abstract
The present study is aimed at characterizing the portal, splanchnic, and systemic circulatory effects of F-180, a new long-acting analog of vasopressin (VP) with selective effect on the vascular (V1) 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 × mmol−1 vs. 9.2 ± 1.2 IU × mmol−1) and four times less potent than arginine VP (614 ± 25 IU × mmol−1). F-180 had negligible antidiuretic potency, resulting in vascular selectivity (V1/V2) 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 (ED50F-180: 0.54 vs. TP: 10.02 nmol × kg−1). At low doses (0.405 nmol × 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 × 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 × kg−1 (28.2% ± 2.7% vs. 8.9% ± 2.7% at 20 minutes;P < .05). F-180 at 0.405 nmol × kg−1 had effects on PP and SMABF similar to a 30-minute intravenous infusion of VP at 10 mU × 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).