The effects of vasopressin on endotoxin-induced attenuation of contractile responses in human gastroepiploic arteries in vitro

We studied the effects of vasopressin on contraction in normal and endotoxin-treated human gastroepiploic arterial rings in vitro. In this tissue, vasopressin (50-500 pg/mL) produced concentration-dependent, endothelium-independent contractions. Vasopressin also potentiated the contraction elicited by 1.0 mu mol/L norepinephrine (NE) in both the presence and absence of endothelium. Endotoxin (10 mu g/mL) attenuated the 1.0 mu mol/L NE-induced contractions, and this attenuation was reversed by 300 mu mol/L N-G-nitro-L-arginine-methyl ester (L-NAME) and by 300 mu mol/L N-G-nitro-L-arginine (L-NoArg). After 12 h endotoxin treatment, the vasopressin-induced contraction was attenuated, and the enhancing effect of vasopressin was diminished. However, both before, and after endotoxin, the enhancement produced by vasopressin was larger than the vasopressin-contraction itself. An antagonist of the vasopressin V1 receptor, 1.0 mu mol/L beta-mercapto[beta,beta-cyclopentamethylenpropionyl1,O-MeTyr(2),Arg(8)]-vasopressin, and an antagonist of V1 + V2 receptor receptor, 1.0 mu mol/L des-Gly(9)-[beta-mercapto-beta,beta-cyclopentamethylenepropionyl1,O-Et-Tyr(2);Val,Arg(8)]-vasopressin, each diminished the vasopressin-induced enhancement of the NE contraction. Implications: The results of our study suggest that, in addition to its direct vasoconstrictor effect, vasopressin strongly enhances the responses to norepinephrine through V1-receptor stimulation and that vasopressin could find a role in the management of endotoxin-induced vasodilation.