Atrial and Brain Natriuretic Peptides
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.
A second natriuretic peptide (brain-type natriuretic peptide; BNP) is a 32-amino acid peptide that is synthesized within 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) 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
- Improve glomerular filtration rate
& filtration fraction
- Inhibit renin release
- ↓ circulating angiotensin II
- ↓ circulating aldosterone
- Systemic vasodilation
- Arterial hypotension
- Reduced venous pressure
- Reduced pulmonary capillary
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.
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 of angiotensin II and aldosterone. This leads to further natriuresis and diuresis. Decreased angiotensin II also contributes to systemic vasodilation and decreased systemic vascular resistance.
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. 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.