DR. PRAMUDJI HASTUTI APT., M.S.

DEPARTMENT OF BIOCHEMISTRY
FACULTY OF MEDICINE
UNIVERSITAS GADJAH MADA
OUTLINES :
1. INTRODUCTION
2. HEART-BRAIN :ANP, BNP, CNP
3. ALDOSTERONE
4. ERYTHROPOIETIN
5. ANGIOTENSIN II
6. ENDOTHELIUM
7. CHEMICAL SUBSTANCE INFLUENCE THE
DIAMETER OF THE ARTERIOLES
 1. INTRODUCTION
- Many hormones regulate cardiorespiratory system
- There are interaction between:

Heart --- brain

Brain --- heart
Heart --- kidney
Kidney --- Heart
Hormones regulate content of blood :
Atrial Natriuretic Peptide
Aldosterone
Erythropoeitin

Hormones regulating blood vessel :

Adrenaline
Noradrenalin
Angiotensin
Vasopressin
Endothelin
Nitric oxide.
 Group of natriuretic peptides.
 ANP, BNP,C-type
 Produced by atrial and ventricular
myocardium, brain
 Produced in response to stretch, increased
end-diastolic pressure
 Physiological action: Acts as diuretic—
natriuretic peptide
 Decrease blood pressure
  ANP
- 28-amino acid (ANP)
- Synthesized, stored, and released by atrial
myocytes in response to atrial distension,
angiotensin II stimulation, endothelin, sympathetic
stimulation and hypernatremia

 First synthesized and stored as prepro-ANP

(151AA) proANP (126 AA)  ANP (28AA)
 Produced in response to stretch  increased end-
diastolic pressure
BNP (brain-type natriuretic peptide; BNP)

- 32-amino acid peptide

- synthesized within ventricles and brain.

• Physiological action: acts as diuretic—natriuretic

peptide
• Decrease blood pressure

Molecule of ANP
Function of
ANP & BNP
Renal
 Dilates the afferent glomerular arteriole, constricts
the efferent glomerular arteriole, increases
glomerular filtration rate (GFR) excretion of
sodium and water increase
 Decreases sodium reabsorption

 Inhibits renin secretion

Adrenal
 Reduces aldosterone secretion by the zona
glomerulosa of the adrenal cortex

Vascular
 Relaxes vascular smooth muscle in arterioles and
venules by cGMP and inhibition of the effects of
catecholamines

Adipose tissue
 Increases the release of free fatty acids from
adipose tissue.
 Increases intracellular cGMP levels that induce the
phosphorylation of a hormone-sensitive lipase and
perilipin A.
Functions of C-type Peptide
 Hormone produced by adrenal cortex
 Steroid hormone
 Production is stimulated by angiotensin II (AT-II)
 Physiological action
Reabsorption of sodium and water, excretion of
potassium and hydrogen
 Site of Action : Kidney (collecting duct)
 sustain extracellular fluid volume by
conserving body sodium.
 secreted in response reduction in
circulating fluid volume
 When body sodium is depleted  fall in
extracellular fluid & plasma volume 
decreases renal arterial blood flow and
pressure.
URINE 14
 Load of potassium from the extracellular fluid
stimulates aldosterone synthesis

 Conversely, potassium depletion lowers aldosterone

secretion

 Potassium stimulates aldosterone synthesis by

depolarizing zona glomerulosa cell membranes
 Released by kidneys in response to decreased O2 or
blood pressure.
 Increases RBC production.

Condition causes decrease tissue oxygenation

1. Anemia Immediately will increase RBCs production
2. Bone marrow destruction
3. High altitudes:
– Partial pressure of oxygen in air less
– Decrease in oxygen transport to tissues
– Tissue hypoxia
– Result : increase production of RBC

4. Cardiac Failure
– Inefficient pumping by heart
– Decreased blood flow to peripheral vessels
– Tissue hypoxia
– Result : increase production of RBC
5. Lung diseases:
– Failure of oxygen absorption in Lungs
– Blood carries less Oxygen
– Tissue hypoxia
– Result : increase production of RBC

 All conditions have one common problem = HYPOXIA

 Response to Hypoxia within minutes

RBC production in 5 days
 Glycoprotein
 Molecular weight 34000
 Sites of production
– Kidneys (main)  adult
– Liver  newborn baby
– Brain, Uterus
 If Erythropoietin production reduced
– Effect of Hypoxia can not be overcome
1. vasoconstriction-dependent hypertension
2. stimulating angiogenesiss,
3. inducing proliferation of smooth muscle fibers
4. increase iron absorption by suppressing the
hormone hepcidin
 5. ANGIOTENSIN II.
Physiological action of angiotensin II:
 Vasoconstriction: Increase blood pressure
 Vasoconstriction of efferent arteriole in kidney:
Increase intraglomerular pressure
 Stimulate vascular growth—mitogen
 Reabsorption of sodium in proximal tubule
 Stimulate production of aldosterone
 Increase sympathetic outflow
 Stimulate thirst: hypothalamus
There are 2 pathways to angiotensin II
production:
 Via RAAS

 Via non-ACE pathways.

 Renin: An enzyme produced by kidney:
juxtaglomerular apparatus.
 In response to: decrease in BP, increase in filtered
sodium load.
 Acts on: Angiotensinogen (produced by liver).
 Converts to angiotensin I.
 Enzyme, produced by endothelium (especially pulmonary
endothelium)

 Converts Angiotensin I to angiotensin II

 3 Genotypes:
 ACE-D/D (190bp)
 ACE-I/I (490 bp)
 ACE-D/I
 (repetitive
sequence of 287
base pairs (bp)
in intron 16 of the
ACE gene)

I  ACE decrease 
ATII decrease
 Various tissues : Heart, blood vessels, uterus,
kidney:
 Able to convert AT I to AT II without renin
 Also: Can produce AT II directly
 Clinical implication:
◦ Drugs: ACE-inhibitors vs AT-II receptor blockers
 > 7 known
 2 of clinical importance:
 AT-II type I: Classic actions of angiotensin II
 AT-II type II: Importance in CV-development

 AT-II blockers: Blocks only AT-II type I receptors

 6. ENDOTHELIUM
Endothelium: 4 groups of functions:

1. Maintains balance between vasoconstriction

and vasodilatation:
 NO, bradykinin, ANP : Vasodilatation
 AT-II, thromboxane A2 : Vasoconstriction
2. Maintains balance between thrombosis and
fibrinolysis:
 Tissue factor (factor III): Thrombosis

 T-PA: Tissue type plasminogen activator:

Fibrinolysis

3. Maintains balance between inflammation and

anti-inflammatory mechanisms.
 Endothelium produces adhesion molecules: ICAM,
PECAM, VECAM etc (Intercellular cell, Platelet
endothelial cell, Vascular cell adhesion molecule)
4. Maintains balance between growth and
apoptosis:
 Angiotensin II: A growth factor, mitogen, causes
hypertrophy of arterial intima
 REGULATION OF ARTERIOLE DIAMETER

- diameter of the arterioles = factor in regulation of

Arterial Blood Pressure
- The plain muscles in the wall of the arterioles
=sphincters
Their contraction  constriction
Their relaxation  dilatation
 7. Chemical substances influencing the
diameter of the arterioles
VASOCONSTRICTOR
a. Adrenaline :  constriction of the arterioles all over
the body except in the heart and skeletal muscles
where they produce vasodilatation, increasing blood
flow to muscles, output of the heart
b. Noradrenalin: stronger vasoconstrictor effect than
adrenaline.
c. Vasopressin (=antidiuretic hormone) secreted by the
posterior pituitary gland  constriction of the
arterioles.
d. Angiotensin II: Potent vasoconstrictor
e. Serotonin:
= vasoconstrictor substance which is released from
blood platelets
= helps to stop bleeding from wounds (local
vasoconstriction of the small vessels in the injured
area)

f. Prostaglandins (PGs):
= hormone like substance
e.g. PGF = vasoconstrictors, (PGA &PGE) = vasodilators.
VASODILATOR

g. Histamine:
= strong vasodilator substance
= released in inflamed or damaged tissues
= also released in allergic reactions.

h. Bradykinine:
=vasodilator substance
= formed in tissues during inflammation or increased
tissue activity.
= mediator of vasodilatation in sweat glands and
digestive glands when they become activated.

END