title: Comparative effects of the novel vasotocin analogue F-180 vs. vasopressin and terlipressin on systemic and splanchnic isolated vessels from portal hypertensive rats.
abstract: F-180 has been proposed as a new vasopressin analogue for the treatment of portal hypertension. This study investigates the contractile profile of F-180 compared to vasopressin and its analogue terlipressin on isolated systemic and splanchnic vessels from sham-operated and partial portal vein ligated (PPVL) rats. F-180 (10(-9)-10(-6) M), vasopressin (10(-11)-10(-8) M) and terlipressin (10(-9)-10(-4) M) induced contraction of the mesenteric vein, aorta, iliac, tail and mesenteric arteries. The order of potency in these vessels was vasopressin (pD2 approximately 9) > F-180 (pD2 approximately 8) > terlipressin (pD2 approximately 6). Significant (P<0.01) differences between sham-operated and PPVL rats were noticed exclusively in the mesenteric vein, being the maximal effect of the three agonists at least twice greater in PPVL rats than in sham-operated rats. The order of sensitivity to the vasoconstrictors in vessels from PPVL rats was aorta < mesenteric artery << iliac artery approximately equal tail artery approximately equal mesenteric vein. The contractile profile of these peptides in each vessel from PPVL animals was quite similar, except in the mesenteric vein and the aorta. F-180 showed higher efficacy (P<0.01) than terlipressin in the mesenteric vein and lower (P<0.05) efficacy than vasopressin in the aorta. These findings suggest the existence of a vasoconstrictor territorial selectivity for vasopressin and its analogues, which could justify the efficacy of these drugs in portal hypertension therapy. In particular, F-180 appears to be a viable alternative to the classic vasopressin analogues.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Valencia, Avda. Blasco Ibañez 15-17, 46010 Valencia, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Ramírez
authors.forename: M A
authors.initials: MA
authors.lastname: Martínez-Cuesta
authors.forename: P
authors.initials: P
authors.lastname: D'Ocon
authors.forename: M A
authors.initials: MA
authors.lastname: Noguera
authors.forename: E
authors.initials: E
authors.lastname: García-Zaragoza
authors.forename: J
authors.initials: J
authors.lastname: Bosch
authors.forename: P
authors.initials: P
authors.lastname: Melin
authors.forename: J V
authors.initials: JV
authors.lastname: Esplugues
mesh_terms: D000818:Animals; D006975:Hypertension, Portal; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D008642:Mesenteric Veins / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077585:Terlipressin; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology
chemical_list: C110660:F-180 vasoconstrictor peptide; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D008236:Lypressin; D000077585:Terlipressin