Atrial Natriuretic Peptide

INTRODUCTION:
  • They are protein hormones secreted by heart muscle cells.
  • Powerful vasodilator.
  • Involved in homeostatic control of body water, Na+,K+ and fat.
  • Released by atrial myocytes in response to high blood pressure.
  • ANP acts to reduce water, Na+, adipose loads on circulatory system, thereby reducing blood pressure.
STRUCTURE:
  • ANP is a 28 amino acid peptide with a 17 amino acid ring in the middle of the molecule.
  • The ring is formed by a disulfide bond between 2 cysteine residues at positions 7 and 23.
  • Cyclic GMP act on Atrial natriuretic peptide
PRODUCTION:
  • Produced, stored and released by cardiac myocytes of atria of heart.
  • Released in response to atrial stretch and a variety of other signals induced by hypervolemia, exercise or caloric restriction.
  • Expressed in ventricle in response to stress induced by increased afterload or injury.
SECRETED IN RESPONSE TO:
  • Atrial distension
  • Sympathetic stimulation of β adrenoceptors
  • Raised sodium concentration
  • Angiotensin-II
  • Endothelin, a powerful vasoconstrictor
RECEPTORS:
  • GC-A
  1. Also known as NPRA/ANPA or NPR1
  • GC-B
  1. Also known as NPRB/ANPB or NPR2 
  • Natriuretic peptide clearance receptor (NPRC)
  1. ANPC or NPR3
PHARMACOLOGICAL EFFECTS:
  • RECEPTOR BINDING
  • REDUCES BLOOD VOLUME
  • REDUCES CARDIAC OUTPUT AND BP
  • Lipolysis is increased and renal sodium reabsorption is decreased
  • Overall effect is to counter the increase in blood pressure and volume caused by renin- angiotensin system
  • RENAL
  • Dilates afferent glomerular arteriole.
  • Constricts efferent glomerular arteriole.
  • Increases pressure in glomerular capillaries, increasing GFR, resulting in greater excretion of sodium and water.
  • Decreases sodium reabsorption in DCT and collecting duct
  • Inhibits renin secretion.
  • Reduces aldosterone secretion.
VASCULAR:
  • Relaxes vascular smooth muscle in arterioles and venules by-
  1. Membrane receptor mediated elevation of vascular smooth muscle cGMP
  2. Inhibition of effect of catecholamine
ADIPOSE TISSUE:
  • Increases release of free fatty acids from adipose tissue
  • Plasma concentration of glycerol and non esterified fatty acids are increased by IV infusion of ANP
CARDIAC:
  • Inhibits maladaptive cardiac hypertrophy
  • Mice lacking cardiac NPRA develop increased cardiac mass and severe fibrosis and die suddenly
ADRENAL:
  • Reduces aldosterone secretion by the zonaglomerulosa of adrenal cortex.
BIOMARKER:
  • ANP and related peptides are used as biomarkers for cardiovascular diseases such as stroke, MI, coronary artery disease and heart failure.
THERAPEUTIC USE:
  • Recombinant human ANP has been approved in Japan to treat patients with heart failure.
DEGRADATION
  • Regulation of effects of ANP is achieved through gradual degradation of peptide by the enzyme neutral endopeptidase (NEP).
  • NEP inhibitors have been developed but not yet been licensed. They maybe clinically useful in treating congestive heart failure.
Exam Question
  • Atrial natriuretic peptide (ANP) inhibits aldosterone synthesis in the adrenal cortex
  • Cyclic GMP act on Atrial natriuretic peptide
  • ANP acts at the Collecting tubule
Don't Forget to Solve all the previous Year Question asked on Atrial Natriuretic Peptide