Diversified cardiovascular actions of six homologous natriuretic peptides (ANP, BNP, VNP, CNP1, CNP3, and CNP4) in conscious eels

Abstract

The natriuretic peptide (NP) family consists of seven paralogs [atrial NP (ANP), brain NP (BNP), ventricular NP (VNP), and C-type NP 1-4 (CNP1-4)] in teleosts, but relative biological activity of the seven NPs has not been comprehensively examined using homologous peptides. In this study, we newly identified CNP3 and CNP4 in eels to use homologous peptides, but the CNP2 gene may have been silenced in this species. The CNP4 gene was expressed exclusively in the brain as CNP1, but the CNP3 gene, from which cardiac ANP, BNP, and VNP were generated by tandem duplication, was most abundantly expressed in the pituitary, suggesting its local action. All NPs induced hypotension dose dependently after intra-arterial injection with a potency order of ANP > VNP > BNP > CNP4 > CNP1 = CNP3. The degree of hypotension was similar at the ventral and dorsal aorta, indicating similar actions on the branchial and systemic circulation. The hypotension induced by cardiac NPs was longer lasting than CNPs, probably because of the difference in preferential receptors. Among cardiac NPs, the hypotensive effect of VNP lasted much longer than those of ANP and BNP, even though VNP disappeared from the blood more quickly than ANP. To analyze the unique effect of VNP, we examined possible involvement of the autonomic nervous system using ANP, VNP, and CNP3. Beta-adrenergic blockade diminished hypotensive effects of all three NPs, but alpha-adrenergic and cholinergic blockade enhanced only the effect of VNP, suggesting a specific mechanism for the VNP action. The NP-induced tachycardia was diminished by all blockers examined. Furthermore, the cardiovascular action of VNP was not impaired by a blocker of NP receptor, HS-142-1. Taken together, the homologous NPs exhibit diverse cardiovascular actions in eels partially through the autonomic nervous system, and the unique VNP action may be mediated by a novel receptor that has not been identified in teleosts.

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

“…A similar decrease in CNP efficacy compared with ANP, BNP and VNP has been observed in the eel cardiovascular system (Nobata et al, 2010), and this may be indicative of a generally lower CNP efficacy in fish. We also showed that rat ANP infusion into trout significantly increased unstressed blood volume and increased vascular compliance (Olson et al, 1997).…”

“…These hormones are produced as pro-peptides and, following cleavage to their mature state, assume a disulfide-linked 17 amino acid ring structure with amino-and carboxy-terminal extensions of variable length. 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).…”

B-Type Natriuretic Peptide Modulates Ghrelin, Hunger, and Satiety in Healthy Men

“…The fact that BNP administration affects only ghrelin and not PYY speaks against a possible mediation of BNP effects via the cholinergic system. This hypothesis is supported by a physiological study in eels revealing that BNP effects are dependent on β-adrenergic blockade but not on cholinergic blockade (20). The fact that BNP does not influence GLP-1, oxyntomodulin, and PP is somewhat expected in this fasting study, as all these peptides are mainly modulated in response to food intake.…”

Cardiovascular function, compliance, and connective tissue remodeling in the turtle,Trachemys scripta, following thermal acclimation

“…Speculatively, this may be due to atrial natriuretic peptide (ANP), which is present in the testudine heart ( 65 ). In mammals and reptiles, ANP is released by cardiomyocytes in response to pressure or volume induced myocardial stretch and has systemic vasodilatory action ( 41 , 49 ); however, it is unclear if the action of ANP is blunted by cold temperatures like some other endocrine functions ( 45 ). Vasodilation is consistent with previous studies that show arterial hypotension following cold acclimation when animals are studied at their acclimation temperatures ( 27 ).…”