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.