Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 237

and skeletal muscle [ 401 ]. It enhances caveolar transcytosis of albumin via its GCa
receptor. Both GCa receptor and cGMP-dependent protein kinase-G1 partly colo-
calize with caveolin-1 in caveola nanodomains (caveolin-1-containing endothelial
membrane rafts).
In addition, ANP lowers the sympathetic tone in the vasculature by direct
suppression of sympathetic signaling from the central nervous system and release of
catecholamines from nerve endings, thereby attenuating tachycardia and vasocon-
striction to reduce postload.
In the kidney, ANP prohormone is cleaved between amino acids 95 and 96, unlike
between amino acids 98 and 99 in the heart. Urodilatin , a 32-amino acid peptide,
is secreted in response to increased mean arterial pressure and blood volume from
cells of the distal tubule and collecting duct in the lumen of the nephron. It then
interacts with receptors at distal segments of the nephron to regulate Na + and water
reabsorption. Intrarenal regulator urodilatin may be more involved in the regulation
of the body's fluid volume and water-electrolyte excretion and circulating ANP in
blood pressure regulation.
Natriuretic peptides and urodilatin can operate in synergy with G-protein-coupled
receptors (e.g., 2-adrenergic receptor in bronchial smooth myocytes) to lower

intracellular calcium concentration, thereby reducing the smooth muscle tone.

β

5.6.1.6 B-Type Natriuretic Peptides

Mature, circulating, 32-amino acid BNP (BNP 77 −− 108 ) is formed from a
134-residue preprohormone cleaved into a prohormone, proBNP (BNP 77 −− 108 ),
predominantly in cardiac ventricles. (Peptide BNP is synthesized in the atria and
ventricle.) Its plasma concentration is a clinical marker for left ventricular overload.
Once proBNP is released into the blood circulation, it is cleaved into a
C-terminal, active fragment — BNP — (plasma half-life 20 mn), and inactive,

76-amino acid, N-terminal fragment (proBNP NT ; plasma half-life

∼

120 mn) [ 402 ].
Ventricular BNP production is transcriptionally regulated by cardiac wall stretch
(volume overload).

∼

5.6.1.7 C-Type Natriuretic Peptides

Member CNP is produced in vascular endothelia and human ventricle. This
22-amino acid peptide has a much wider distribution than that of ANP and BNP
hormones. Two mature forms derived from a 126-amino acid preprohormone (pre-
proCNP) processed into a 103-amino acid prohomone (proCNP; CNP 1 −− 103 )[ 402 ].
They include CNP 53 (CNP 51 −− 103 ), which predominates in tissues, and CNP 22
(CNP 82 −− 103 ) mainly in plasma and cerebrospinal fluid.
This hormone regulates the local vascular tone. It precludes angiotensin-2-
stimulated release of endothelin [ 402 ]. Conversely, endothelin antagonizes CNP
action.