Ganong's Review of Medical Physiology, 23rd Edition

358 SECTION IVEndocrine & Reproductive Physiology

renin–angiotensin system in a feedback fashion (Figure 22–25).
A drop in ECF volume or intra-arterial vascular volume leads to
a reflex increase in renal nerve discharge and decreases renal
arterial pressure. Both changes increase renin secretion, and the
angiotensin II formed by the action of the renin increases the
rate of secretion of aldosterone. The aldosterone causes Na+
and, secondarily, water retention, expanding ECF volume and
shutting off the stimulus that initiated increased renin secretion.
Hemorrhage stimulates ACTH and renin secretion. Like
hemorrhage, standing and constriction of the thoracic inferior
vena cava decrease intrarenal arterial pressure. Dietary sodium
restriction also increases aldosterone secretion via the renin–
angiotensin system (Figure 22–26). Such restriction reduces
ECF volume, but aldosterone and renin secretion are increased
before any consistent decrease in blood pressure takes place.
Consequently, the initial increase in renin secretion produced
by dietary sodium restriction is probably due to a reflex
increase in the activity of the renal nerves. The increase in cir-

culating angiotensin II produced by salt depletion upregulates

the angiotensin II receptors in the adrenal cortex and hence

increases the response to angiotensin II, whereas it down-regu-

lates the angiotensin II receptors in the blood vessels.

ELECTROLYTES & OTHER FACTORS

An acute decline in plasma Na+ of about 20 mEq/L stimulates

aldosterone secretion, but changes of this magnitude are rare.

However, the plasma K+ level need increase only 1 mEq/L to

stimulate aldosterone secretion, and transient increases of this

magnitude may occur after a meal, particularly if it is rich in

K+. Like angiotensin II, K+ stimulates the conversion of cho-

lesterol to pregnenolone and the conversion of deoxycorticos-

terone to aldosterone. It appears to act by depolarizing the cell,

which opens voltage-gated Ca2+ channels, increasing intra-

cellular Ca2+. The sensitivity of the zona glomerulosa to an-

giotensin II and consequently to a low-sodium diet is

decreased by a low-potassium diet.

In normal individuals, plasma aldosterone concentrations

increase during the portion of the day that the individual is

carrying on activities in the upright position. This increase is

due to a decrease in the rate of removal of aldosterone from

the circulation by the liver and an increase in aldosterone

secretion due to a postural increase in renin secretion. Indi-

viduals who are confined to bed show a circadian rhythm of

aldosterone and renin secretion, with the highest values in the

early morning before awakening.

Atrial natriuretic peptide (ANP) inhibits renin secretion

and decreases the responsiveness of the zona glomerulosa to

angiotensin II (see Chapter 39).

The mechanisms by which ACTH, angiotensin II, and K+

stimulate aldosterone secretion are summarized in Table 22–7.

FIGURE 22–24 Changes in adrenal venous output of
steroids produced by angiotensin II in nephrectomized
hypophysectomized dogs.

8

Change in

17-hydroxy-

corticoid

(μg/min)

Change in

aldosterone

output

(ng/min)

6

4

2

0

25

20

15

10

5

0

0.042 0.0830.1670.42 1.67

Dose of angiotensin II

(μg/min)

No. of dogs (5)* (2) (8) (7) (7)

*Aldosterone values in 3 dogs

FIGURE 22–25 Feedback mechanism regulating aldosterone secretion. The dashed arrow indicates inhibiition.

Angiotensin-

converting enzyme

Angiotensinogen Renin

Angiotensin I

Angiotensin II

Aldosterone Decreased Na+

(and water) excretion

Increased extracellular

fluid volume

Increased renal arterial

mean pressure, decreased

discharge of renal nerves

Juxtaglomerular

apparatus

Adrenal

cortex