SUMMARYNatriuretic peptides (NPs) and their receptors (NPRs) comprise an evolutionarily conserved signaling system with profound physiological effects on vertebrate renal and cardiovascular systems. Some NPs (ANP, BNP and VNP) are primarily of cardiac origin whereas CNP is common in the brain. In mammals, non-traditional sites of NPs synthesis, BNP in brain and CNP in atrium, appear to have complementary actions. In the present study, trout were chronically adapted to freshwater (FW) (a volume-loading, salt-depleting environment), saltwater (SW) (a volume-depleting, salt-loading environment), FW and fed a high-salt diet (FW-HSD) (a volume-and salt-loading regime) or acutely volume depleted or expanded by hemorrhage or infusion with dialyzed plasma to perturb volume homeostasis. The responses of brain and atrial BNP and CNP mRNA, pro-peptide, NPR-A and NPR-B were evaluated using quantitative PCR and western analysis. Brain pro-BNP and NPR-A was increased in FW-HSD trout and decreased in SW trout. Brain pro-CNP was largely unaffected whereas NPR-B mRNA was increased in FW-HSD trout. Atrial CNP, although produced at lower levels than other cardiac NPs, was markedly elevated in chronically (FW-HSD) and acutely volume expanded trout (dialyzed-plasma infusion) whereas decreased in hemorrhaged trout. These findings indicate that non-traditional NP synthesis sites in the trout probably complement the broad hypovolemic and hypotensive actions of traditional (cardiac) NP synthesis sites in response to volume expansion but not to plasma osmolarity. This supports the hypothesis that the piscine and mammalian NP systems are fundamentally similar and appear to protect the heart from volume overload.