Nitric Oxide and Vasopressin Expression during Sepsis

Abstract

We investigated the role of centrally produced NO on hypothalamic arginine vasopressin (AVP) expression and release and on cardiovascular response during experimental sepsis. Male Wistar rats were i.c.v injected with the non‐selective NO synthase (NOS) inhibitor L‐NAME, or aminoguanidine (AG), a selective inhibitor of the inducible isoform (iNOS). After 30min sepsis was induced by cecal ligation and puncture (CLP) causing increases in NO plasma levels and heart rate (HR) and a reduction in arterial pressure (MAP) and AVP expression ratio (AVPR) in the supraoptic (SON) and paraventricular (PVN) nuclei. AVP plasma levels (AVPp) increased, but only in the early phase. L‐NAME pretreatment, reduced NO production and increased MAP and did not change HR. AVPp further increased in the early phase but decreased in the late phase while AVPR decreased in both phases. AG i.c.v injected did not change substantially the increase of NO plasma levels but increased MAP in the initial phase of sepsis. AVPR increased only in the SON, and AVPp remained all time elevated. These results show that increased central NO production differentially inhibits AVPR in SON and PVN, contributing to basal AVPp and hypotension in the late phase of sepsis.Financial support: FAPESP