1

2

INTRODUCTION

• They are protein hormones secreted by heart musclecells.• Powerful vasodilator.• Involved in homeostatic control of body water, Na+,K+

and fat.• Released by atrial myocytes in response to high bloodpressure.• ANP acts to reduce water, Na+, adipose loads oncirculatory system, thereby reducing blood pressure.

3

STRUCTURE

•ANP is a 28 amino acid peptide with a 17 amino acid ring in the middle of themolecule.•The ring is formed by a disulfide bond between 2 cysteine residues at positions7 and 23.•ANP is closely related to BNP and CNP which all share the same amino acidring.

4

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 byhypervolemia, exercise or caloric restriction.• Expressed in ventricle in response to stress induced by increased afterload orinjury.

5

SECRETED IN RESPONSE TO-

Atrial distension

Sympathetic stimulation of β adrenoceptors

Raised sodium concentration

Angiotensin-II

Endothelin, a powerful vasoconstrictor

6

RECEPTORS

GC-A

•Also known as NPRA/ANPA or NPR1

GC-B

•Also known as NPRB/ANPB or NPR2

Natriuretic peptide clearance receptor (NPRC)

•ANPC or NPR3

7

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 byrenin- angiotensin system

8

1. 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.

9

2. VASCULAR

Relaxes vascular smooth muscle in arterioles and venules by-1. Membrane receptor mediated elevation of vascular smooth

muscle cGMP2. Inhibition of effect of catecholamine

10

•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

3. ADIPOSE TISSUE

11

• Inhibits maladaptive cardiac hypertrophy

• Mice lacking cardiac NPRA develop increased cardiac mass and severe fibrosis and die suddenly

4. CARDIAC

12

• Reduces aldosterone secretion by the zonaglomerulosa of adrenal cortex.

13

5. ADRENAL

• ANP and related peptides are used as biomarkers for cardiovascular diseases such as stroke, MI, coronary artery disease and heart failure.

14

BIOMARKER

• Recombinant human ANP has been approved in Japan to treat patients with heart failure.

15

THERAPEUTIC USE

• 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.

DEGRADATION

16

• www.wikipedia.com

• www.google.com

• www.ncbi.nlm.nih.gov

• www.cvpharmacology.com

• www.sciencedirect.com

REFERENCES

17

18