Comparative effects of the novel vasotocin analogue F-180 vs. vasopressin and terlipressin on systemic and splanchnic isolated vessels from portal hypertensive rats

F-180 has been proposed as a new vasopressin analogue for the treatment of portal hypertension. This study investigates the contractile profile of F-1 80 compared to vasopressin and its analogue terlipressin on isolated system ic and splanchnic vessels from sham-operated and partial portal vein ligate d (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 (pD(2) similar to9) > F- 180 (pD(2) similar to8) > terlipressin (pD(2) similar to6). Significant (P <0.01) differences betwee n sham-operated and PPVL rats were noticed exclusively in the mesenteric ve in, being the maximal effect of the three agonists at least twice greater i n PPVL rats than in sham-operated rats. The order of sensitivity to the vas oconstrictors in vessels from PPVL rats was aorta < mesenteric artery < ili ac artery congruent to tail artery congruent to mesenteric vein. The contra ctile 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 exi stence of a vasoconstrictor territorial selectivity for vasopressin and its analogues, which could justify the efficacy of these drugs in portal hyper tension therapy. In particular, F-180 appears to be a viable alternative to the classic vasopressin analogues.