The response of non-traditional natriuretic peptide production sites to salt and water manipulations in the rainbow trout

Abstract

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.

Endogenous vascular synthesis of B-type and C-type natriuretic peptides in the rainbow trout

“…A strong argument has been made that the piscine NP system is principally responsive to volume, and hence the physiological progenitor to the mammalian NP system (Farrell and Olson, 2000;Johnson and Olson, 2008;Johnson and Olson, 2009a;Johnson and Olson, 2009b). The results from the present study further extend the multiple functional similarities between the piscine and mammalian NP systems and indicate that the production of NPs in the vasculature is a fundamental property of the NP system that is found throughout vertebrates.…”

“…These peptides are likely stored as pro-hormones in the vasculature (as they are in the heart), because the processed (mature) mRNA levels of BNP and CNP in all blood vessels examined were significantly reduced compared with atrial BNP and brain CNP, respectively. In the atrium, which is a non-traditional production site for CNP (Inoue et al, 2003b;Johnson and Olson, 2009b), CNP mRNA was found in an un-spliced pre-mRNA form (introncontaining) where a previously unreported intronic sequence was identified (and submitted to GenBank as CNP intron-1). Alternatively, in both the brain and vasculature, CNP mRNA was found in the fully processed (intron-removed) form.…”

“…EBA, CMA and ACV), will effectively accomplish this. Pre-branchial NP synthesis in the vasculature, such as the VA and the heart (Johnson and Olson, 2009a;Johnson and Olson, 2009b), are likely modulators of R G (and to a lesser extent P VA ), the primary determinants of afterload. Clearly, exogenous CNP can effectively reduce R G (Fig.5) and thereby lower cardiac afterload.…”

“…CNP, which lacks the carboxy-terminal extension, is widely considered the ancestral NP (Inoue et al, 2003a), and has been identified in multiple variant forms known as CNP1-4 in medaka, pufferfish and eel (Inoue et al, 2003a;Kawakoshi et al, 2004;Nobata et al, 2010). CNP is found in taxa from agnathans to humans, and appears to be ubiquitously expressed in the central nervous system, and to a lesser extent in the atrium (Arimura et al, 1991;Inoue et al, 2003b;Johnson and Olson, 2009b).…”

“…As the mammalian endothelium is a local source of CNP and CNP has been identified in trout brain and heart (Inoue et al, 2003b;Johnson and Olson, 2009b) and in fish plasma (Gary Anderson et al, 2005;, it is likely that fish possess a vascular NP component as well. Therefore, the principal aims of the present study were twofold: (1) to identify the endogenous production of NP(s) in the vasculature of rainbow trout, and (2) to assess the effects of CNP on the trout cardiovascular system in vivo.…”