REGULATION OF

CIRCULATORY SYSTEM

Department of Physiology Faculty of Medicine

Hasanuddin University
Makassar
2002
 INTRODUCTION
 In humans, several circulation regulatory
mechanisms have evolved
 Circulatory adjustments are affected by
altering cardiac output, changing the
diameter of resistance vessels or blood
volume
 The regulatory mechanisms synergize each
other and adjust vascular responses
throughout the body
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 REGULATORY MECHANISM
OF CIRCULATORY SYSTEM

 Local regulatory mechanisms

 Systemic regulation by hormones
 Systemic regulation by nervous system
 Long term regulation by kidneys

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 Local Regulatory Mechanisms

 Based on the capacity of tissues to regulate

their own blood flow (autoregulation)
 Most vascular beds have an intrinsic capacity
to compensate for moderate changes in
perfusion pressure
 Autoregulation consist of two mechanism:
– Myogenic regulation
– Metabolic regulation
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 Local Regulatory Mechanisms

 The smooth muscle of the walls of the

arterioles, contracts in response to increase in
transmural pressure and relaxes in response
to a decrease in transmural pressure
 Increase in longitudinal pressure induced
vasodilatation caused by the endothelium-
derived relaxing factors (EDRF) such as NO

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Excitation-contraction Coupling in Vascular Smooth Muscle

Ca2+

Sarcolemma
G Pl-C

PiP2 IP3 + DG Ca2+

Sarcoplasmic
reticulum
Ca2+
Ca2+

ATP
Ca2+ + Calmodulin
Ca2+ pump

Contraction
 Flow-induced Vasodilatation in Isolated Arteriole
1.0

0.9
Arteriolar diameter

0.8

0.7

0.6

0.5
0 20 40 60 80
Pressure gradient (cm H2O)
 Local Regulatory Mechanisms

 Endothelial cells produce endothelium-derived

contracting factor (EDCF) and endothelium-
derived relaxing factor (EDRF)
 EDCF include endothelins (ET), thromboxane
A2, Angiotensin II
 EDRF include nitrit oxide (NO), prostacyclin
 Adenosine, ANP, and histamine produce
relaxation independent of the endothelium
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 Local Regulatory Mechanisms

 According to metabolic mechanism, blood

flow is governed by metabolic activity of the
tissue
 Any intervention that results in an O2 supply
that is inadequate for requirements gives rise
to the formation of vasodilator metabolites
 CO2, lactate, H+, adenosine, histamin have
been proposed as a vasodilator metabolites
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 Hormonal Regulation

 Vasodilator hormones:
– bradykinin
– vasoactive intestinal peptide (VIP)
– atrial natriuretic peptide (ANP)
– adrenomedullin (AM)
 Vasoconstrictor hormones:
– epinephrine and norepinephrine
– vasopressin
– angiotensin II

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 Regulation by Nervous System

 Autonomic Nervous System

– Sympathetic nerve
– Parasympathetic nerve
 Central Nervous System (Vasomotor
area)
 Baroreceptors and Neural Reflexes

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 Regulation by Nervous System

Sympathetic Nerve
 All blood vessels except capillaries and venule
receive motor nerve fibers from sympathetic
nerve
 The fibers to resistance vessels regulate tissue
blood flow and arterial pressure
 The fibers to capacitance vessels regulate the
volume of blood stored in the veins

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 Factors affecting the diameter of the arterioles
Constriction Dilatation

Local factors
- Autoregulation
- Decreased local temperature
Endothelial products
- ET-1
- Thromboxan A
Circulatingh hormones
- Epinephrine (except in skeletal
muscle and liver)
- Angiotensin II, vasopressin
-CO2, decreased O2
-K+, lactate, adenosine
- local temperature, local pH
- NO
- Bradykinin
- Prostacyclin
- Epinephrine in skeletal
muscle and liver
- Histamine, ANP, VIP

Neural factors
- Sympathetic and vasomotor - Sympathetic and vasomotor
center activity center activity, cholinergic discharge
 Regulation by Nervous System
Vasomotor Control
 Consist of groups of neurons in the medulla
oblongata that mediate sympathetic discharge to
blood vessels and heart
 Afferent fibers to the vasomotor area not only from
blood vessels but also from other parts of the
nervous system and lungs
 Variations in blood pressure is adjusted by
feedback control of vasomotor area, vessels
diameter and baroreceptors
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Factors affecting the activity of the vasomotor area

Direct stimulation
CO2
Hypoxia
Excitatory inputs
From cortex via hypothalamus
From pain pathways and muscle
From carotid and aortic chemoreceptors
Inhibitory inputs
From cortex via hypothalamus
From lungs
From carotid, aortic,and cardiopulmonary baroreceptors
 Feedback control of blood pressure

Baroreceptors

Blood pressure Vasomotor area

Heart rate

Stroke volume

Vessel diameter
 Regulation by Nervous System
Neural reflexes, Baroreceptors and Chemoreceptors
 Somatosympathetic reflex caused by pain
 Baroreceptors
– Dilatation of arterioles and veins
– Slowing heart rate and decreased heart contractions
 Chemoreceptors
– Hypoxia and hypercapnia both stimulate vasomotor
area
– The direct effect of hypoxia and hypercapnia to blood
vessels is vasodilatation
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 Long term Regulation by Kidneys

 Two determinants of the long-term regulation of

arterial blood pressure:
– Renal output of salt and water
– Renin-angiotensin system
 Salt increases the extracellular fluid volume by:
– increased osmolality of the body fluids
– increased antidiuretic hormone secretion

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 Intake NaCl 
Tekanan darah  Angiotensinogen
Volume CES  Renin
Stres/Trauma
Angiotensin I

Makula Densa, Baroreseptor, Susunan Saraf Simpatis ACE

Angiotensin II

Sel Juxtaglomerular

Adrenal Ginjal P. Darah Jantung Otak Faktor

Pertumbuhan

Aldosteron Vasokonstriksi Vasokonstriksi

Reabsorbsi Aliran darah Tahanan Kontraksi ADH Proliferasi

Na Reabsorbsi Perifer Simpatis otot polos
Na
 SUMMARY OF THE INTEGRATED
REGULATION OF BLOOD PRESSURE

 Rapid acting blood pressure control (within seconds or

minute): 1) baroreceptor feedback mechanism, 2)
vasomotor mechanism and 3) chemoreceptor mechanism
 Intermediate time period (within 30 min to several
hours): 1) renin-angiotensin system, 2) stress-relaxation
mechanism and 3) shift of fluid through the capillary
walls in and out of the circulation
 Long-term mechanism (days to years): 1) renal-blood
volume pressure control and 2) renin-angiotensin system

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