ARGININE-VASOPRESSIN INHIBITS INTERLEUKIN-1-BETA-STIMULATED NITRIC-OXIDE AND CYCLIC GUANOSINE-MONOPHOSPHATE PRODUCTION VIA THE V-1 RECEPTORIN CULTURED RAT VASCULAR SMOOTH-MUSCLE CELLS

Background It has been reported that various vasoactive substances mod ulate cytokine stimulated nitric oxide (NO) production in many cell ty pes. Objective To examine the effects of arginine vasopressin (AVP) on the production of NO and cyclic GMP (cGMP), and on inducible nitric o xide synthase (INOS) in cultured rat vascular smooth muscle cells (VSM C). Design Because VSMC possess the V-1 receptor which causes vascular contraction and respond to various cytokines for producing NO, we use d rat VSMC and selected interleukin-1 beta (IL-1 beta) as a potent sti mulator of NO production among various cytokines. We also measured cGM P production, which is the final mediator of NO-induced vascular relax ation, in order to evaluate the physiologic meaning of the present stu dy, 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 imm unoassay, INOS messenger RNA expression was analyzed by Northern blott ing, Results AVP inhibited IL-1 beta-induced nitrite production in a d ose- and time-dependent manner with concomitant changes in intracellul ar cGMP contents. On the other hand, AVP did not affect nitrite and cG MP production in the absence of IL-1 beta. Inhibition of nitrite and c GMP 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 b y the oxytocin (OXT) receptor antagonist [d(CH2)(5), Tyr(Me)(2), Orn(8 )]-Vasotocin. Administration of the V-1 receptor antagonist or OXT rec eptor antagonist alone did not affect IL-1 beta-stimulated nitrite and cGMP production, Although administration of AVP inhibited IL-1 beta-i nduced INOS messenger RNA expression, administration of the V-1 recept or antagonist but not of the OXT receptor antagonist reversed this inh ibition. Conclusion It is suggested that AVP inhibits IL-1 beta-induce d NO and cGMP production via the V-1 receptor but not via the OXT rece ptor in VSMC, AVP can cause vascular contraction not only through dire ct action but also through indirect action by inhibiting NO production under some inflammatory conditions.