Biomedical Engineering Reference
In-Depth Information
Prohormone ANP
1
−−
126
generates 4 peptide hormones that regulate blood
pressure and maintain plasma volume: (1)
long-acting natriuretic peptide
(LANP;
amino acids 1-30 of ANP prohormone [ANP
1
−−
30
]); (2)
vessel dilator
(amino
acids 31-67 of ANP prohormone [ANP
31
−−
67
]); (3)
kaliuretic peptide
(amino acids
79-98 of ANP prohormone [ANP
79
−−
98
]); and (4)
atrial natriuretic peptide
(amino
acids 99-126 of ANP prohormone [ANP
99
−−
126
)
]). On the other hand, the Bnp and
Cnp genes synthesize a single known peptide hormone.
These peptide hormones circulate in blood. Plasma concentrations of vessel
dilator and LANP are 17- to 22-fold higher than that of ANP, 33- to 48-fold larger
than that of BNP, 124- to 177-fold greater than that of CNP, and 170- to 177-fold
higher than that of urodilatin that is synthesized only in kidney (amino acids 95-126
of ANP prohormone [ANP
95
−−
126
)
]).
Clearance of natriuretic peptides from the blood circulation involves receptor
binding, uptake especially by the clearance receptor NP
3
, and metabolism in target
cells, and degradation by zinc metallopeptidases — neutral peptidases — in vascular
and renal tubular cells and excretion via urine.
Atrial and B-type natriuretic peptides are synthesized predominantly in atria and
the left ventricle, respectively, in response to elevated wall tension. Plasma levels of
natriuretic peptides correlate positively with cardiac filling pressures.
Atriocardiomyocytes are long, slender, and poor in T tubules. Atrial cardiomy-
ocytes contain small granules, especially in the right atrium. These granules secrete
atrial natriuretic peptide immediately when atriocardiomyocytes are excessively
stretched. Ventricular cardiomyocytes synthesize B-type natriuretic peptide. Levels
of BNP reflect long-term overload [
404
].
5.6.1.3
Natriuretic Peptide Receptors
Three types of receptors (NP
1
-NP
3
; Vol. 3 - Chap. 6. Receptors) have been
described for the natriuretic peptides (Table
5.8
). Factors ANP and BNP target
guanylate cyclases (NP
1
-NP
2
) that produce cyclic guanosine monophosphate.
Mediator cGMP then acts on cGMP-dependent protein kinases PKG, cGMP-gated
ion channels, and cGMP-regulated phosphodiesterases.
5.6.1.4
Angiotensin-2 and Endothelin-1
Angiotensin-2 is not only a vasoconstrictor and mitogenic peptide, but also an
inducer of atrial natriuretic peptide expression via extracellular signal-related kinase
in ventriculomyocytes.
69
69
Hypertrophied heart releases natriuretic peptides ANP and BNP. Regulator ANP has both direct
and indirect effects on the heart. It inhibits cardiomyocyte growth by lowering activation of ERK1
and ERK2 and upregulating phosphatase MKP1. It reduces hemodynamic load by educing diuresis
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