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 micromol/L norepinephrine (NE) in both the presence and absence of endothelium. Endotoxin (10 microg/mL) attenuated the 1.0 micromol/L NE-induced contractions, and this attenuation was reversed by 300 micromol/L N(G)-nitro-L-arginine-methyl ester (L-NAME) and by 300 micromol/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 micromol/L beta-mercapto-[beta,beta-cyclopentamethylenpropionyl1,O-MeTyr2+ ++,Arg8]-vasopressin, and an antagonist of V1 + V2 receptor receptor, 1.0 micromol/L des-Gly9-[beta-mercapto-beta,beta-cyclopentamethylenepropionyl1 ,O-Et-Tyr2,Val,Arg8]-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.