Biological Functions
Natriuretic peptides are naturally occurring substances
in the body that oppose the activity of the renin–
angiotensin system. The natriuretic peptide family consists
of atrial natriuretic peptide (ANP), brain natriuretic
peptide (BNP), and C-type natriuretic peptide
(CNP). All three natriuretic peptides are synthesized
from cleavage of a larger precursor polypeptide. In the
ventricles and brain, the synthesis of BNP predominates;
ANP is synthesized by cardiac myocytes predominately
in the atria; and CNP is synthesized in the brain,
blood vessels, and kidney.
All three peptides exhibit similar biological activities;
however, they differ in the potency of individual responses.
The target organs of the natriuretic peptides include
the kidneys, blood vessels, brain, and adrenal
cortex. These peptides exhibit potent diuretic, natriuretic,
and vasodilator effects. Natriuretic peptides promote
endothelial permeability and the movement of
water from the intravascular to the extravascular space.
In the kidney, natriuretic peptides increase the glomerular
filtration rate through vasodilation of the afferent
arteriole and constriction of the efferent arteriole, inhibition
of the reabsorption of sodium in the proximal
and distal tubule, and inhibition of renin synthesis. In
the brain, natriuretic peptides are involved in the regulation
of central control of cardiovascular functions.
These biological effects of natriuretic peptides come together
to reduce venous return and total peripheral resistance,
thereby improving cardiac performance and
reducing blood pressure.
The release of ANP from the heart is regulated
acutely by stretch of atrial myocytes and has been used
as a marker for cardiovascular diseases, including congestive
heart failure and hypertension. In addition, recent
results demonstrate an increase in the circulating
concentration of ANP following stroke and linkage of
the ANP gene to patients who have strokes. Two types
of atrial natriuretic receptors have been identified in
target tissues, including guanylate cyclase–linked receptors
(subdivided into types A and B) and a receptor
thought to serve as a clearance mechanism for the removal
of circulating ANP. Analogues that act as ANP
agonists are being developed for use in hypertension
and congestive heart failure.
In addition, a new class of drugs, termed vasopeptidase
inhibitors, inhibit the enzymatic activity of ACE
and neutral endopeptidase, the enzyme responsible for
the breakdown of natriuretic peptides.The end result is
a reduction in the synthesis of angiotensin II and an increase
in the circulating level of natriuretic peptides
such as ANP. Omapatrilat, a vasopeptidase inhibitor, is
under study for the treatment of hypertension and congestive
heart failure.
