Arginine vasopressin inhibits interleukin-1 beta-stimulated nitric oxide and cyclic guanosine monophosphate production via the V-1 receptor in cultured rat vascular smooth muscle cells

Background It has been reported that various vasoactive substances modulate cytokine stimulated nitric oxide (NO) production in many cell types. Objective To examine the effects of arginine vasopressin (AVP) on the production of NO and cyclic GMP (cGMP), and on inducible nitric oxide synthase (INOS) in cultured rat vascular smooth muscle cells (VSMC). Design Because VSMC possess the V-1 receptor which causes vascular contraction and respond to various cytokines for producing NO, we used rat VSMC and selected interleukin-1 beta (IL-1 beta) as a potent stimulator of NO production among various cytokines. We also measured cGMP production, which is the final mediator of NO-induced vascular relaxation, in order to evaluate the physiologic meaning of the present study, Methods VSMC were incubated with test agents for 24 h except for a time-course study. Nitrite as a stable end product of NO was measured in the medium. Intracellular cGMP contents were assayed by enzyme immunoassay, INOS messenger RNA expression was analyzed by Northern blotting, Results AVP inhibited IL-1 beta-induced nitrite production in a dose- and time-dependent manner with concomitant changes in intracellular cGMP contents. On the other hand, AVP did not affect nitrite and cGMP production in the absence of IL-1 beta. Inhibition of nitrite and cGMP production by AVP was reversed by administration of the specific V-1 receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)-tyrosine]-Arg(8)-vasopressin) but not by the oxytocin (OXT) receptor antagonist [d(CH2)(5), Tyr(Me)(2), Orn(8)]-Vasotocin. Administration of the V-1 receptor antagonist or OXT receptor antagonist alone did not affect IL-1 beta-stimulated nitrite and cGMP production, Although administration of AVP inhibited IL-1 beta-induced INOS messenger RNA expression, administration of the V-1 receptor antagonist but not of the OXT receptor antagonist reversed this inhibition. Conclusion It is suggested that AVP inhibits IL-1 beta-induced NO and cGMP production via the V-1 receptor but not via the OXT receptor in VSMC, AVP can cause vascular contraction not only through direct action but also through indirect action by inhibiting NO production under some inflammatory conditions.