Ganong's Review of Medical Physiology, 23rd Edition

676 SECTION VIII Renal Physiology

receptor does not trigger any intracellular change and is in-
stead a clearance receptor that removes natriuretic peptides
from the bloodstream and then releases them later, helping to
maintain a steady blood level of the hormones.

SECRETION & METABOLISM

The concentration of ANP in plasma is about 5 fmol/mL in
normal humans ingesting moderate amounts of NaCl. ANP se-
cretion is increased when the ECF volume is increased by infu-
sion of isotonic saline and when the atria are stretched. BNP
secretion is increased when the ventricles are stretched. ANP
secretion is also increased by immersion in water up to the neck
(Figure 39–13), a procedure that counteracts the effect of grav-
ity on the circulation and increases central venous and conse-
quently atrial pressure. Note that immersion also decreases the
secretion of renin and aldosterone. Conversely, a small but
measurable decrease in plasma ANP occurs in association with
a decrease in central venous pressure on rising from the supine
to the standing position. Thus, it seems clear that the atria re-
spond directly to stretch in vivo and that the rate of ANP secre-
tion is proportional to the degree to which the atria are
stretched by increases in central venous pressure. Similarly,
BNP secretion is proportional to the degree to which the ven-
tricles are stretched. Plasma levels of both hormones are elevat-
ed in congestive heart failure, and their measurement is seeing
increasing use in the diagnosis of this condition.
Circulating ANP has a short half-life. It is metabolized by
neutral endopeptidase (NEP), which is inhibited by thior-
phan. Therefore, administration of thiorphan increases circu-
lating ANP.

Na, K ATPase-INHIBITING FACTOR

Another natriuretic factor is present in blood. This factor pro-
duces natriuresis by inhibiting Na, K ATPase and raises rather
than lowers blood pressure. Current evidence indicates that it
may well be the digitalis-like steroid ouabain and that it comes
from the adrenal glands. However, its physiologic significance
is not yet known.

DEFENSE OF SPECIFIC

IONIC COMPOSITION

Special regulatory mechanisms maintain the levels of certain

specific ions in the ECF as well as the levels of glucose and other

nonionized substances important in metabolism (see Chapter

1). The feedback of Ca2+ on the parathyroids and the calcitonin-

secreting cells to adjust their secretion maintains the ionized

calcium level of the ECF (see Chapter 23). The Mg2+ concentra-

tion is subject to close regulation, but the mechanisms control-

ling Mg+ metabolism are incompletely understood.

The mechanisms controlling Na+ and K+ content are part

of those determining the volume and tonicity of ECF and

have been discussed above. The levels of these ions are also

dependent on the H+ concentration, and pH is one of the

major factors affecting the anion composition of ECF. This

will be discussed in Chapter 40.

FIGURE 39–12 Diagrammatic representation of natriuretic
peptide receptors. The NPR-A and NPR-B receptor molecules have in-
tracellular guanylyl cyclase domains, whereas the putative clearance re-
ceptor, NPR-C, has only a small cytoplasmic domain. CM, cell membrane.

ECF

Cytoplasm

Guanylyl

cyclase

domain

CM

NPR-A NPR-B NPR-C

FIGURE 39–13 Effect of immersion in water up to the neck

for 3 h on plasma concentrations of ANP, PRA, and aldosterone.

(Modified and reproduced with permission from Epstein M, et al: Increases in

circulating atrial natriuretic factor during immersion-induced central hypervolaemia

in normal humans. Hypertension 1986;4 [Suppl 2]:593.)

15

10

5

Immersion

0

3

2

1

0

10

5

0

012345

Time (hrs)

Aldosterone (ng/dL)

PRA (ng AI/mL/hr)

ANP (fmol/mL)