Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 39Regulation of Extracellular Fluid Composition & Volume 675

family has been named C-type natriuretic peptide (CNP)
because it was the third in the sequence to be isolated. It con-
tains 22 amino acid residues (Figure 39–11), and there is also
a larger 53-amino-acid form. CNP is present in the brain, the
pituitary, the kidneys, and vascular endothelial cells. However,
very little is present in the heart and the circulation, and it
appears to be primarily a paracrine mediator.

ACTIONS

ANP and BNP in the circulation act on the kidneys to increase
Na+ excretion, and injected CNP has a similar effect. They ap-
pear to produce this effect by dilating afferent arterioles and

relaxing mesangial cells. Both of these actions increase glo-

merular filtration (see Chapter 38). In addition, they act on the

renal tubules to inhibit Na+ reabsorption. Other actions in-

clude an increase in capillary permeability, leading to extrava-

sation of fluid and a decline in blood pressure. In addition,

they relax vascular smooth muscle in arterioles and venules.

CNP has a greater dilator effect on veins than ANP and BNP.

These peptides also inhibit renin secretion and counteract the

pressor effects of catecholamines and angiotensin II.

In the brain, ANP is present in neurons, and an ANP-con-

taining neural pathway projects from the anteromedial part of

the hypothalamus to the areas in the lower brain stem that are

concerned with neural regulation of the cardiovascular sys-

tem. In general, the effects of ANP in the brain are opposite to

those of angiotensin II, and ANP-containing neural circuits

appear to be involved in lowering blood pressure and promot-

ing natriuresis. CNP and BNP in the brain probably have

functions similar to those of ANP, but detailed information is

not available.

NATRIURETIC PEPTIDE RECEPTORS

Three different natriuretic peptide receptors (NPR) have been

isolated and characterized (Figure 39–12). The NPR-A and

NPR-B receptors both span the cell membrane and have cyto-

plasmic domains that are guanylyl cyclases. ANP has the

greatest affinity for the NPR-A receptor, and CNP has the

greatest affinity for the NPR-B receptor. The third receptor,

NPR-C, binds all three natriuretic peptides but has a markedly

truncated cytoplasmic domain. Some evidence suggests that it

acts via G proteins to activate phospholipase C and inhibit

adenylyl cyclase. However, it has also been argued that this

FIGURE 39–10 ANP granules (g) interspersed between
mitochondria (m) in rat atrial muscle cell. G, Golgi complex; N, nu-
cleus. The granules in human atrial cells are similar (× 17,640).
(Courtesy of M Cantin.)

NNN

GG

gg mm

FIGURE 39–11 Human ANP, BNP, and CNP. Top: Single-letter codes for amino acid residues aligned to show common sequences (col-
ored). Bottom: Shape of molecules. Note that one cysteine is the carboxyl terminal amino acid residue in CNP, so there is no carboxyl terminal
extension from the 17-member ring. (Modified from Imura H, Nakao K, Itoh H: The natriuretic peptide system in the brain: Implication in the central control of
cardiovascular and neuroendocrine functions. Front Neuroendocrinol 1992;13:217.)

ANP BNP CNP

HOOC

H 2 N

HOOC

HOOC

ANP

BNP

CNP

H 2 N

H 2 N

SLRRSSCFGGRMDRIGAQSGLGCNSFRY

SPKMVQGSGCFGRKMDRISSSSGLGCKVLRRH

GLSKGCFGLKLDRIGSMSGLGC

128

132

122