Natriuretic peptide system, biological effects
Natriuretic peptides are a family of structurally related hormonal
factors. Atrial natriuretic peptide (ANP) and type B natriuretic peptide
(BNP) are secreted by the atria and cardiac ventricles. Type C
natriuretic peptide (CNP) is the most highly expressed natriuretic
peptide in the brain, but is also highly expressed in chondrocytes and
endothelial cells. Neutral neprilisin endopeptidase (NEP) is the enzyme
that metabolizes natriuretic peptides. Natriuretic peptides mediate
different physiological effects through interaction with specific
guanylyl cyclase (GC) receptors that cause intracellular cGMP
production. The main physiological effects are natriuresis / diuresis
and peripheral vasodilation, inhibition of the
renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous
system (SNS) but other important biological functions have been
highlighted in recent times. In particular, some studies have
demonstrated an antifibrotic and anti-inflammatory action associated
with natriuretic peptides. The natriuretic peptide type C (CNP), a
member of the natriuretic peptide family, by selective binding to the
transmembrane receptor guanylyl cyclase (GC)-B, mediates different
biological effects in various organs. (37) CNP is expressed in a wide
variety of tissues, such as the vascular endothelium, heart, bones and
adrenal glands. (38) (39)(40)(41) CNP plays an important role in the
regulation of local vascular tone, and has been shown to have mainly
cardioprotective, antihypertrophic (42) and antifibrotic (43) effects.
Recently, CNP has been shown to have protective effects against
inflammatory and fibrotic reactions (44)(45). In vivo tests have
revealed that CNP attenuates acute lipopolysaccharid-induced lung
lesions (LPS) (46). CNP also regulates the secretion of inflammatory
cytokines (47)(48).
In the inflammatory phase, expression levels of various chemokines,
cytokines and growth factors are high and these mediators exert their
profibrotic activity through the activation and proliferation of
fibroblasts (49). Considering the pathophysiological importance of
fibroblast activation in pulmonary fibrosis (50), and the above
mentioned biological effects, it is suggested that there is a direct
effect on pulmonary fibroblasts by natriuretic peptides. These insights
suggest the use of therapeutic agents that increase the concentration of
these peptides in the more severe stages of COVID-19 infection when a
fibrotic pulmonary state is present. In association with evidence of
antifibrotic and antihyperproliferative effects, the studies also show
direct antiffiammatory effects mediated by the action of natriuretic
peptides. In particular, some studies associate the BNP peptide with an
important inhibitory effect on NALP3 inflammasome activation, which is
related to BNP-induced downregulation of NF-kB and ERK1/2 activation.
The data indicate a powerful anti-inflammatory and immunomodulatory role
for this peptide. (51) These effects mediated by natriuretic peptides
suggest an important role in COVID-19 infection.