In determining mean jugular venous pressure, one assumes that the filling
pressure of the right atrium and right ventricle mirror that of the left atrium and
left ventricle. This relationship is usually correct. Thus, a mean jugular venous
pressure greater than 10 cm H2O usually indicates volume overload, while a low
jugular venous pressure (i.e., less than 5 cm H2O) usually indicates hypovolemia.
But there are important, notable exceptions to this relationship. First, acute left
ventricular failure (as may be caused by a myocardial infarction) may significantly
raise the pulmonary capillary wedge pressure without raising the mean right atrial
and jugular venous pressures. Second, pulmonary hypertension, tricuspid
insufficiency, or stenosis may be associated with elevated mean right atrial and
jugular venous pressures while leaving the left heart pressures unaffected. In
using the mean jugular venous pressure in clinical practice, the physician must
correlate this bedside measurement with the other information gained from the
history and physical examination.
Natriuretic peptides are peptide hormones that are synthesized by the heart, brain and other organs.
The release of these peptides by the heart is stimulated by atrial and ventricular distension, as well as
by neurohumoral stimuli, usually in response to heart failure. The main physiological actions of
natriuretic peptides is to reduce arterial pressure by decreasing blood volume and systemic vascular
resistance.
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 stimulation (beta-adrenoceptormediated). Therefore, elevated levels of ANP are
found during hypervolemic states (elevated blood volume), which occurs in congestive heart
failure. ANP is first synthesized and stored in cardiac myocytes as prepro-ANP, which is then cleaved
to pro-ANP and finally to ANP. ANP is the biologically active peptide.
A second natriuretic peptide (brain-type natriuretic peptide; BNP) is a 32-amino acid peptide that is
synthesized largely by the ventricles (as well as in the brain where it was first identified). BNP is first
synthesized as prepro-BNP, which is then cleaved to pro-BNP and finally to BNP. Like ANP, BNP is
released by the same mechanisms that release ANP, and it has similar physiological
actions. Proteolysis of pro-BNP (108 amino acids) results in BNP (32 amino acids) and the N-terminal
piece of pro-BNP (NT-pro-BNP; 76 amino acids). Both BNP and NT-pro-BNP are sensitive, diagnostic
markers for heart failure in patients.
Neutral endopeptidase (NEP; also called neprilysin) is a circulating enzyme that degrades
natriuretic peptides. Therefore, inhibition of this enzyme increases circulating levels of natriuretic
peptide and potentiates their effects.
Cardiovascular and Renal Effects
Cardiovascular and Renal
Actions of Natriuretic Peptides
Natriuresis
Diuresis
Improve glomerular filtration rate
& filtration fraction
Inhibit renin release
o ↓ circulating angiotensin II
o ↓ circulating aldosterone
Systemic vasodilation
Arterial hypotension
Reduced venous pressure
Reduced pulmonary capillary
wedge pressure
Natriuretic peptides (NPs) are involved in the long-term regulation of sodium and water balance, blood
volume and arterial pressure. There are two major pathways of natriuretic peptide actions: 1)
vasodilator effects, and 2) renal effects that leads to natriuresis and diuresis.
NPs directly dilate veins (increase venous compliance) and thereby decrease central venous
pressure, which reduces cardiac output by decreasing ventricular preload. NPs also dilate arteries,
which decreases systemic vascular resistance and systemic arterial pressure. Chronic elevations of
NPs appear to decrease arterial blood pressure primarily by decreasing systemic vascular resistance.
The mechanism of systemic vasodilation involves NP receptor-mediated elevations in vascular smooth
muscle cGMP as well as attenuation of sympathetic vascular tone. This latter mechanism may involve
NPs acting on sites within the central nervous system as well as through inhibition of norepinephrine
release by sympathetic nerve terminals.
NPs affect the kidneys by increasing glomerular filtration rate (GFR) and filtration fraction, which
produces natriuresis (increased sodium excretion) and diuresis (increased fluid excretion). These
renal effects of NPs are potassium sparing unlike most diuretic drugs that are used to induce
natriuresis and diuresis in patients.
A second renal action of NPs is that they decrease renin release, thereby decreasing circulating levels
ofangiotensin II and aldosterone. This leads to further natriuresis and diuresis. Decreased angiotensin
II also contributes to systemic vasodilation and decreased systemic vascular resistance.
Taken together, these actions of NPs decrease blood volume, arterial pressure, central venous
pressure, pulmonary capillary wedge pressure, and cardiac output. To summarize, natriuretic
peptides serve as a counter-regulatory system for the renin-angiotensin-aldosterone system.
A recombinant human BNP, or nesiritide, is approved for use in the acute treatment of
decompensated congestive heart failure caused by systolic dysfunction. A new class of drugs that are
neutral endopeptidase (NEP) inhibitors have been shown to be efficacious in animal models of heart
failure. These drugs inhibit neutral endopeptidase, the enzyme responsible for the degradation of ANP,
and thereby elevate plasma levels of ANP. NEP inhibition is particularly effective in animal models of
heart failure when the drug is combined with an ACE inhibitor.
