Natriuretic Hormones in Brain Function

Abstract

Natriuretic hormones (NH) include three groups of compounds: the natriuretic peptides (ANP, BNP and CNP), the gastrointestinal peptides (guanylin and uroguanylin), and endogenous cardiac steroids. These substances induce the kidney to excrete sodium and therefore participate in the regulation of sodium and water homeostasis, blood volume, and blood pressure (BP). In addition to their peripheral functions, these hormones act as neurotransmitters or neuromodulators in the brain. In this review, the established information on the biosynthesis, release and function of NH is discussed, with particular focus on their role in brain function. The available literature on the expression patterns of each of the NH and their receptors in the brain is summarized, followed by the evidence for their roles in modulating brain function. Although numerous open questions exist regarding this issue, the available data support the notion that NH participate in the central regulation of BP, neuroprotection, satiety, and various psychiatric conditions, including anxiety, addiction, and depressive disorders. In addition, the interactions between the different NH in the periphery and the brain are discussed.

Heads and Tails of Natriuretic Peptides: Neuroprotective Role of Brain Natriuretic Peptide

“…Our experimental study confirmed the clinical findings as animals with higher blood levels of hBNP before ischemia presented significant infarct volume reduction and a better sensorimotor recovery. These results were also in line with a previous experimental study19 in an animal model of intracerebral hemorrhage and traumatic brain injury that describes that the intravenous administration of nesiritide (a human recombinant form of BNP) improved the cerebral blood flow and reduced the inflammation and brain injury reflected in a better functional outcome, supporting the hypothesis that NPs can act as an endogenous protective mechanism in the brain against injury 1…”

“…NPs play an important physiological function in the body as endocrine and paracrine molecules involved in the control of water and therefore in the regulation of arterial pressure 1, 26. Experimental evidences have also described the protective effect of NPs in cerebral injury18, 19, 20, 21; however, although the study of NPs (mainly BNP) has been focused as a biomarker of heart failure3, 26 and biomarker of cardioembolic stroke,5, 6, 7, 8, 9, 10 a clinical analysis about the protective effect of BNP in stroke that confirms the beneficial effect of these molecules has not been performed so far.…”

“…BNP receptors are widely expressed in the brain, and BNP has been found in different cerebral regions such as hypothalamus or cerebral cortex,1, 15, 17, 28 for instance. However, BNP‐mRNA has not been detected in cerebral tissue, suggesting a peripheral origin of this peptide 1, 29, 30.…”

“…Like atrial natriuretic peptide, BNP is released in heart stress situations. C‐type natriuretic peptide, contrary to atrial natriuretic peptide and BNP, does not have direct natriuretic activity 1, 2…”

“…In brain, expression of NP receptors have been described in regions such as the cerebral cortex, limbic area, preoptic–hypothalamic regions, cerebellum, or brainstem,1, 15, 16, 17 and there are experimental evidences that show NPs may exert neuroprotective effects in cultured cells and in vivo studies 18, 19, 20, 21…”