The Kidneys and Regulation of Water and Inorganic Ions
The other internal input to the juxtaglomerular cells is
via the macula densa, which, as noted earlier, is located near
the ends of the ascending loops of Henle (see Figure 14–2).
The macula densa senses the sodium concentration in the
tubular ﬂ uid ﬂ owing past it. A decreased salt concentration
causes increased renin secretion. Therefore, in an indirect way,
this mechanism is sensitive to changes in sodium intake. If
salt intake is low, less sodium is ﬁ ltered and less appears at the
macula densa. Conversely, a high salt intake will cause a very
low rate of release of renin. In addition, macula densa sodium
decreased due to decreased GFR and, therefore, tubular ﬂ ow
rate. This input therefore also results in increased renin release
at the same time that the sympathetic nerves and intrarenal
baroreceptors are doing so (see Figure 14–22).
The importance of this system is highlighted by the
considerable redundancy in the control of renin secretion.
Furthermore, as illustrated in Figure 14–22, the various mech-
anisms can all be participating at the same time.
By helping to regulate sodium balance and thereby
plasma volume, the renin-angiotensin system contributes to
the control of arterial blood pressure. However, this is not the
only way in which it inﬂ uences arterial pressure. Recall from
Chapter 12 that angiotensin II is a potent constrictor of arte-
rioles all over the body and that this effect on peripheral resis-
tance increases arterial pressure.
Drugs have been developed to manipulate the angio-
tensin II and aldosterone components of the system. ACE
inhibitors such as lisinopril reduce angiotensin II produc-
tion from angiotensin I by inhibiting angiotensin-converting
enzyme. Angiotensin II receptor blockers such as losartan
prevent angiotensin II from binding to its receptor on tar-
get tissue (e.g., vascular smooth muscle and the adrenal cor-
tex). Finally, there are drugs such as eplerenone that block
the binding of aldosterone to its receptor in the kidney.
Although these classes of drugs have different mechanisms
of action, they are all effective in the treatment of hyperten-
sion. This highlights that many forms of hypertension can be
attributed to the failure of the kidney to adequately excrete
sodium and water.
Atrial Natriuretic Peptide
Another controller is
atrial natriuretic peptide (ANP),
known as atrial natriuretic factor (ANF) or hormone (ANH).
Cells in the cardiac atria synthesize and secrete ANP. ANP
acts on several tubular segments to inhibit sodium reabsorp-
tion. It can also act on the renal blood vessels to increase GFR,
which further contributes to increased sodium excretion. ANP
also directly inhibits aldosterone secretion, which leads to an
increase in sodium excretion. As would be predicted, the secre-
tion of ANP increases when there is an excess of sodium in
the body, but the stimulus for this increased secretion is not
alterations in sodium concentration. Rather, using the same
logic (only in reverse) that applies to the control of renin and
aldosterone secretion, ANP secretion increases because of the
expansion of plasma volume that accompanies an increase in
body sodium. The speciﬁ c stimulus is increased atrial distension
Interaction of Blood Pressure and Renal Function
An important input controlling sodium reabsorption is arte-
rial blood pressure. We have previously described how the arte-
rial blood pressure constitutes a signal for important reﬂ exes
(involving the renin-angiotensin system and aldosterone) that
inﬂ uence sodium reabsorption. Now we are emphasizing that
arterial pressure also acts locally on the tubules themselves.
Speciﬁ cally, an
in arterial pressure
sorption and thereby increases sodium excretion in a process
Sodium and H
Cortical collecting ducts
Sodium and H
Renal juxtaglomerular cells
Activity of renal
GFR, which causes
flow to macula densa
to macula densa
(see Fig. 14–20)
Pathways by which decreased plasma volume leads, via the
renin-angiotensin system and aldosterone, to increased sodium
reabsorption by the cortical collecting ducts and hence to decreased
What would be the effect of denervation (removal of sympathetic
neural input) of the kidneys on sodium and water excretion?
Answer can be found at end of chapter.