CHAPTER 6 • NEUROHUMORAL CONTROL OF THE HEART AND CIRCULATION
139
circulating angiotensin II. Primary hyperal-
dosteronism, caused by an adrenal tumor that
secretes large amounts of aldosterone, increases
arterial pressure through its effects on renal
sodium retention. This increases blood volume,
cardiac output, and arterial pressure. In this
condition, renin release and circulating angio-
tensin II levels are usually depressed because of
the hypertension. In heart failure, circulating
angiotensin II increases in response to sympa-
thetic activation and decreased renal perfusion.
Therapeutic
manipulation of the renin-
angiotensin-aldosterone system has become
important in treating hypertension and heart
failure. ACE inhibitors and AT: receptor block-
ers effectively decrease arterial pressure, ven-
tricular afterload, blood volume, and hence
ventricular preload, and they inhibit and reverse
cardiac and vascular remodeling that occurs
during chronic hypertension and heart failure.
Note that local, tissue-produced angioten-
sin may play a significant role in cardiovascular
pathophysiology. Many tissues and organs,
including the heart and blood vessels, can
produce renin and angiotensin II, which have
actions directly within the tissue. This may
explain why ACE inhibitors can reduce arte-
rial pressure and reverse cardiac and vascular
remodeling (e.g., diminish hypertrophy) even
in individuals who do not have elevated circu-
lating levels of angiotensin II. In hypertension
and heart failure, for example, tissue ACE
activity is often elevated, and this may be
an important target for the pharmacologic
actions of ACE inhibitors.
CASE 6-1
A 56-year-old male patient is found
to have an arterial pressure of
190/115 mm Hg. Two years earlier, he
was normotensive. Diagnostic tests
reveal bilateral renal artery stenosis.
Describe the mechanisms by which this
condition elevates arterial pressure.
Atrial Natriuretic Peptide
Atrial
natriuretic
peptide
(ANP)
is
a
28-amino acid peptide that is synthesized,
stored, and released by atrial myocytes in
response to atrial distension, angiotensin II
stimulation, endothelin, and sympathetic stim-
ulation (P-adrenoceptor mediated). Therefore,
elevated levels of ANP are found during condi-
tions such as hypervolemia and congestive heart
failure, both of which cause atrial distension.
ANP is involved in the long-term regula-
tion of sodium and water balance, blood vol-
ume, and arterial pressure (Fig. 6.12). Most of
its actions are the opposite of angiotensin II,
and therefore
ANP is a counterregulatory system
4- Aldosterone
Atrial distension
Sympathetic
stimulation
Angiotensin II
Endothelin
iS V R
CO
\
/
Arterial
I
Blood
* Pressure
* Volume
NEP
Degradation
i
Angiotensin II
Renin
Release
Natriuresis^
Diuresis
FIGURE 6.12
Formation and cardiovascular/renal actions of atrial natriuretic peptide (
ANP
). ANP, which
is released from cardiac atrial tissue in response to atrial distension, sympathetic stimulation, increased
angiotensin II, and endothelin, functions as a counterregulatory mechanism for the renin-angiotensin-
aldosterone system. ANP decreases renin release, angiotensin II and aldosterone formation, blood volume,
central venous pressure, and arterial pressure.
NEP,
neutral endopeptidase;
GFR,
glomerular filtration rate;
CVP,
central venous pressure; CO, cardiac output;
SVR,
systemic vascular resistance.
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