Natriuretic Peptides
Natriuretic peptides are naturally
occurring substances in the body that oppose the activity of the renin–
angiotensin system. The natriuretic peptide family con-sists of atrial
natriuretic peptide (ANP), brain natri-uretic 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 predomi-nates; ANP is synthesized by cardiac myocytes
predom-inately in the atria; and CNP is synthesized in the brain, blood
vessels, and kidney.
All three peptides exhibit
similar biological activi-ties; however, they differ in the potency of
individual re-sponses. The target organs of the natriuretic peptides in-clude
the kidneys, blood vessels, brain, and adrenal cortex. These peptides exhibit
potent diuretic, natri-uretic, and vasodilator effects. Natriuretic peptides
pro-mote endothelial permeability and the movement of water from the
intravascular to the extravascular space. In the kidney, natriuretic peptides increase
the glomeru-lar filtration rate through vasodilation of the afferent arteriole
and constriction of the efferent arteriole, inhi-bition 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 regu-lation of central
control of cardiovascular functions. These biological effects of natriuretic
peptides come to-gether to reduce venous return and total peripheral
re-sistance, 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 con-gestive heart failure and
hypertension. In addition, re-cent 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
recep-tors (subdivided into types A and B) and a receptor thought to serve as a
clearance mechanism for the re-moval 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 vasopepti-dase 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 in-crease in the circulating level of natriuretic
peptides such as ANP. Omapatrilat, a vasopeptidase inhibitor, is under study
for the treatment of hypertension and con-gestive heart failure.
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