Human Physiology, 14th edition (2016)

462 Chapter 14

observation that immersion in water (which increases venous

return) causes increased diuresis. But how is this accom-

plished? Experiments suggest that the increased water excre-

tion under conditions of high blood volume or venous return

is at least partly due to an increase in the excretion of Na^1 in

the urine, or natriuresis ( natrium 5 sodium;  uresis 5 mak-

ing water).

Increased Na^1 excretion (natriuresis) may be produced by

a decline in aldosterone secretion, but there is evidence that

there is a separate hormone that stimulates natriuresis. This

natriuretic hormone would thus be antagonistic to aldosterone

and would promote Na^1 and water excretion in the urine in

response to a rise in blood volume. A polypeptide hormone

with these properties, identified as atrial natriuretic peptide

(ANP), is produced by the atria of the heart.

When a person floats in water, there is an increase in

venous return to the heart. This (like an increase in blood vol-

ume) stretches the atria, thereby stimulating the release of

ANP. In addition, ADH secretion from the posterior pituitary

is inhibited, due to sensory information traveling to the hypo-

thalamus in the vagus nerves from stretch receptors in the left

atrium. Increased ANP, together with decreased ADH, leads to

a greater excretion of salt and water in the urine. This works as

a negative feedback correction to lower the blood volume and

thus maintain homeostasis ( fig. 14.13 ).

The renin-angiotensin-aldosterone system can also work
in the opposite direction: high salt intake, leading to high
blood volume and pressure, normally inhibits renin secre-
tion. With less angiotensin II formation and less aldoste-
rone secretion, less salt is retained by the kidneys and more
is excreted in the urine. Unfortunately, many people with
chronically high blood pressure may have normal or even
elevated levels of renin secretion. In these cases, the intake
of salt must be lowered to match the impaired ability to
excrete salt in the urine.

Atrial Natriuretic Peptide

Scientists have long known that a rise in blood volume, or
an increased venous return for any other reason, leads to
increased urine production ( diuresis ). In fact, it is a common

Figure 14.12 The renin-angiotensin-aldosterone

system. This system helps to maintain homeostasis through

the negative feedback control of blood volume and pressure.

(ACE  5  angiotensin-converting enzyme.)

Stimuli

Negative feedback

responses

Blood pressure

Blood flow to kidneys

Juxtaglomerular

apparatus

in kidneys

Angiotensinogen Angiotensin I

ACE

Adrenal cortex

Vasoconstriction

of arterioles

Salt and water

retention by kidneys

Blood volume Blood pressure

Renin

Angiotensin II

Aldosterone

Sensor

Integrating center

Effector

CLINICAL APPLICATION

Angiotensin converting enzyme inhibitors ( ACE inhibitors )

are drugs that prevent the conversion of angiotensin I to

angiotensin II, reducing the ability of angiotensin II to stimu-

late vasoconstriction. This action promotes vasodilation and

a lowering of the total peripheral resistance, thereby low-

ering blood pressure. ACE inhibitors—including captopril,

enalapril, and lisinopril —help to treat hypertension, heart fail-

ure, stroke, and potential kidney failure, and aid the survival

of people who have had myocardial infarctions. Angiotensin

receptor blockers ( ARBs )—including telmisartan, losar-

tan, and valsartan —inhibit the binding of angiotensin II to

its receptors on vascular smooth muscles, thereby reducing

vasoconstriction. This promotes vasodilation and a lower-

ing of the blood pressure, much like the actions of the ACE

inhibitors, and so ARBs have similar medical uses.

Clinical Investigation CLUES

Mark was diagnosed with essential hypertension, for

which the physician prescribed an ACE inhibitor.

• What is ACE, and what does it do?


• How does an ACE inhibitor help to lower the blood
  pressure?