Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 235

Tabl e 5. 8. Natriuretic peptide receptors and rank of affinity of the peptides to these receptors
(Source: [ 402 ]). Most natriuretic peptides are secreted from cardiomyocytes in response to stretch
of atrial or ventricular walls. The effects of cardiac natriuretic peptides include natriuresis,
diuresis, and inhibition of the activities of several regulators, such as the renin-angiotensin-
aldosterone system, endothelins, cytokines, and the sympathetic nervous system. Active peptides
target natriuretic peptide receptors, NP 3 acting as a clearance receptor upon action of neutral
endopeptidase. Hormone DNP activates NP 1 rather than NP 2 receptor. Messenger cGMP is the
second messenger formed by a ctivated NP 1 and NP 2 guanylate cyc lases.

Receptor Rank of affinity

NP 1 ANP ≥ BNP CNP

NP 2 CNP > ANP ≥ BNP

NP 3 ANP > BNP > CNP

On the other hand, atrial natriuretic peptide opposes the reduction of angiotensin-
converting enzyme-2 (ACE2) synthesis initiated by angiotensin-2 and endothelin-
1(Fig. 5.10 )[ 405 ]. In cardiomyocytes, ACE2 responds to various vasoactive
peptides and hormones. It preferentially forms heptapeptide angiotensin 1 − 7 from
angiotensin-2. 70 Conversely, in cardiomyocytes and cardiac fibroblasts, angiotensin-
2 lowers ACE2 synthesis and activity, thereby preventing the conversion into
angiotensin 1 − 7 .
Endothelin-1 also significantly attenuates ACE2 expression in cardiomyocytes.
Both angiotensin-2 and endothelin-1 that are released from cardiomyocytes in
response to mechanical strain and/or stress, work via extracellular signal-regulated
kinases ERK1 and ERK2.

5.6.1.5 A-Type Natriuretic Peptides

Once it is released, the ANP propeptide is cleaved by a heart-specific
transmembrane serine peptidase corin into a 28-amino acid C-terminal active form
— ANP — and a 98-amino acid, N-terminal, inactive form (proANP 1 −− 98 ]).
The latter is processed by peptidases to generate several active peptides:
(1) long-acting natriuretic peptide , i.e., proANP 1 −− 30 ;(2) vessel dilator , i.e.,

and natriuresis. Factor ANP binds to its receptors NPR-A and NPR-B to stimulate guanylate
cyclase and generate cGMP.
70 Enzyme ACE2 also hydrolyzes dynorphin-A and apelin. It is expressed in both endothelial and
smooth muscle cells of coronary vessels as well as in cardiomyocytes and cardiac fibroblasts. Level
of ACE2 rises in heart failure and ischemic and idiopathic dilated cardiomyopathy. Angiotensin 1 − 7
operates via a specific receptor AT(1-7). Angiotensin 1 − 7 hampers cardiomyocyte growth. Whereas
ANP lowers effects of ERK1 and ERK2 via cGMP and MKP1, angiotensin 1 − 7 decreases activity
of ERK1 and ERK2 via cAMP.