Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 39

Regulation of Extracellular Fluid Composition & Volume 673

characteristic of caveolae. In rodents, two different but closely
related AT
1
subtypes, AT
1A
and AT
1B
, are coded by two sepa-
rate genes. The AT
1A
subtype is found in blood vessel walls,
the brain, and many other organs. It mediates most of the
known effects of angiotensin II. The AT
1B
subtype is found in
the anterior pituitary and the adrenal cortex. In humans, an
AT
1
receptor gene is present on chromosome 3. There may be
a second AT
1
type, but it is still unsettled whether distinct
AT
1A
and AT
1B
subtypes occur.
There are also AT
2
receptors, which are coded in humans
by a gene on the X chromosome. Like the AT
1
receptors, they
have seven transmembrane domains, but their actions are dif-
ferent. They act via a G protein to activate various phos-
phatases which in turn antagonize growth effects and open K

channels. In addition, AT
2 receptor activation increases the
production of NO and therefore increases intracellular cyclic
3,5-guanosine monophosphate (cGMP). The overall physio-
logic consequences of these second-messenger effects are
unsettled. AT 2 receptors are more plentiful in fetal and neona-
tal life, but they persist in the brain and other organs in adults.
The AT 1 receptors in the arterioles and the AT 1 receptors
in the adrenal cortex are regulated in opposite ways: an
excess of angiotensin II down-regulates the vascular recep-
tors, but it up-regulates the adrenocortical receptors, making
the gland more sensitive to the aldosterone-stimulating effect
of the peptide.

THE JUXTAGLOMERULAR APPARATUS

The renin in kidney extracts and the bloodstream is produced
by the juxtaglomerular cells (JG cells). These epitheloid cells
are located in the media of the afferent arterioles as they enter
the glomeruli (Figure 39–9). The membrane-lined secretory

granules in them have been shown to contain renin. Renin is

also found in agranular lacis cells that are located in the junc-

tion between the afferent and efferent arterioles, but its signif-

icance in this location is unknown.

At the point where the afferent arteriole enters the glomeru-

lus and the efferent arteriole leaves it, the tubule of the neph-

ron touches the arterioles of the glomerulus from which it

arose. At this location, which marks the start of the distal con-

volution, there is a modified region of tubular epithelium

called the macula densa (Figure 39–9). The macula densa is in

close proximity to the JG cells. The lacis cells, the JG cells, and

the macula densa constitute the juxtaglomerular apparatus.

REGULATION OF RENIN SECRETION

Several different factors regulate renin secretion (Table 39–2),

and the rate of renin secretion at any given time is determined

by the summed activity of these factors. One factor is an intra-

renal baroreceptor mechanism that causes renin secretion to

decrease when arteriolar pressure at the level of the JG cells in-

creases and to increase when arteriolar pressure at this level

falls. Another renin-regulating sensor is in the macula densa.

Renin secretion is inversely proportional to the amount of Na+

and Cl– entering the distal renal tubules from the loop of Henle.

Presumably, these electrolytes enter the macula densa cells via

the Na–K–2Cl– transporters in their apical membranes, and the

increase in some fashion triggers a signal that decreases renin

secretion in the juxtaglomerular cells in the adjacent afferent ar-

terioles. A possible mediator is NO, but the identity of the signal

remains unsettled. Renin secretion also varies inversely with the

plasma K+ level, but the effect of K+ appears to be mediated by

the changes it produces in Na+ and Cl– delivery to the macula

densa.

FIGURE 39–9 Left: Diagram of glomerulus, showing the juxtaglomerular apparatus. Right: Phase contrast photomicrograph of afferent ar-
teriole in an unstained, freeze-dried preparation of the kidney of a mouse. Note the red blood cell in the lumen of the arteriole and the granulated
juxtaglomerular cells in the wall. (Courtesy of C Peil.)

Juxtaglomerular

cells

Lacis

cells

Macula

densa

Afferent

arteriole

Efferent

arteriole

Glomerulus

Renal

nerves