Prof.

Edgaras Stankeviius MD, PhD

Blood vessels: closed delivery
system
It is a delivery system that
begins and ends at the
heart
Arteries: carry blood from
the heart to
microcirculation
Capillaries: site for
exchange of gases, water,
nutrients, waste products.
Veins: carry blood toward
the heart
Blood vessels:
3 types:
Arteries
Cappillaries
Veins

2 sub-types:
Arterioles
Venules

Total length:
~100 000 km
 Vessel layers
Tunica intima
Endothelium lines the lumen of all vessels
Vessels larger then 1 mm have basement
membrane
Tunica media
Smooth muscle and sheets of elastin
Function: vasoconstriction and vasodilation
Tunica externa (adventitia)
Collagen fibers (reinforcement)
Lager vessels contain vasa vasorum
Arterial structure
 Blood flow is driven by a constant
pressure
During heart beats blood fills the arteries
Compliance of large arteries reduces
pressure pulsations
Almost no pressure pulsations in
capillaries
Tissue blood flow is mainly continuous
 Hemodynamics
Blood flows continuously
Downstream cross-sectional area of an
arterial bed increases (from aorta to
capillaries x 1000 times)
Blood flow speed
decreases downstream
due to increased
cross-sectional area
 Arterial pulse can be recorded and
analysed. The recording is called a
sphygmogram.

Arterial pulse can be recorded on arteries:

close to the heart (central sphygmogram) or

on peripheral arteries (peripheral sphygmogram)

Arterial pulse is a peripheral expression of the hearts
mechanical activity perceived by palpating the arteries

Main factors affecting the pulse pressure:

1. The stroke volume output of the heart
2. The compliance of the arterial tree
3. The character of blood ejection during systole
 Amplification of the pressure waveform moving from the aorta to the radial artery

Greater compliance = slower velocity

Great compliance Low compliance

Pressure

Carmel M. McEniery et al. Eur Heart J 2014;35:1719-1725

Published on behalf of the European Society of Cardiology. All rights reserved. The Author
2014. For permissions please email: journals.permissions@oup.com.
 Pulse Wave Velocity (PWV) is a measure of
arterial stiffness, or the rate at which pressure
waves move down the vessel. It has been
established as a highly reliable prognostic
parameter for cardiovascular function
As blood flows through the vessels of the circulatory system, it
moves out of the left ventricle and into the aorta where it is then
pushed through the rest of the circulatory system. During
systole, the contraction of the left ventricle and the ejection of
blood into the ascending aorta acutely dilates the aortic wall and
generates a pressure wave that moves along the arterial tree.
The velocity of this movement gives a measurement of arterial
compliance.

With age, or due to changes in the arterial wall, these vessels

become stiffer and the speed at which the pressure wave moves
through the system is increased.
Augmented arterial stiffness is expected to increase with ageing,
this process of vascular ageing may be accelerated in the
presence of cardiovascular risk factors.

Fonseca et al., 2014

Main determinants which are thought to
contribute to the arterial blood pressure:
1. Blood Volume: This is the volume of blood available in the
system. More volume means that the vessels and the heart
have to work harder to pump.
2. Overall Compliance: The elastic characteristics of the
vessels contribute to the overall pressure. Expansion of
arteries and veins will help lower the blood pressure.
3. Cardiac Output: CO is related to two other factors: heart
rate and stroke volume. When heart rate is fast, CO is
increased and when stroke volume is high, CO is also
increase. When CO increases, it is obvious that the arterial
pressure will increase.
4. Peripheral Resistance: The resistance of the arteries is
related to the Overall Compliance Characteristic. When
peripheral resistance increase, the overall compliance is
decrease and thus the increase of arterial blood pressure.
Palpation and
Auscultation methods
 Blood volume distribution

Pulmonary
Arteries and Vessels 12%
arterioles 15%
Heart 8%
Capillaries 5%

Veins and venules 60%

 Blood pressure in veins

4.6 mmHg

5-6 mmHg

12-18 mmHg
Effect of gravity in veins
 Blood flows in veins due to:
Pumping action of the heart atrial
pressure drops during ventricular
ejection

Thoracic pump during inspiration

intrathoracic pressure falls up to -6
mmHg

Muscle pump valves prevent reverse

flow, the blood moves towards the
heart

Pulsations of the large arteries

15% of blood plasma drains out from the interstitial fluid
into nearby lymphatic vessels. The fluid in the lymph is
similar in composition to the interstitial fluid.
The lymph fluid passes through lymph
nodes before it returns to the heart via
the vena cava. Lymph nodes are
specialized organs that filter the lymph
by percolation through a maze of
connective tissue filled with white
blood cells. The white blood cells
remove infectious agents, such as
bacteria and viruses, to clean the
lymph before it returns to the
bloodstream. After it is cleaned, the
lymph returns to the heart by the
action of smooth muscle pumping,
skeletal muscle action, and one-way
valves joining the returning blood near
the junction of the venae cavae
entering the right atrium of the heart.
http://www.craighartbasso.com
Lymphatic capillaries.
Fluid from the capillaries moves into the interstitial space and lymph capillaries by
diffusion down a pressure gradient and also by osmosis.
Out of 7,200 liters of fluid pumped by the average heart in a day, over 1,500 liters is
filtered.
Missing Link Between Brain & Immune System Discovered

Nature 523, 337341 (16 July 2015)

Impaired lymphatic drainage

Lymphat Res Biol. 2003; 1(2): 121132.

 Changes in pressure driving
forces (either hydrostatic or
osmotic) and in the size of
"pores" or intercellular clefts will
alter exchange

Net driving force

 Regulation of the circulation
I. Local (myogenic, metabolic, endothelium-
derived factors)
II. Systemic:
Nervous
Humoral

Short term
Long term
Regulation of the local blood circulation
- Tissues and organs within the body are able to
intrinsically regulate, to varying degree, their own blood
supply in order to meet their metabolic and functional
needs.

Myogenic autoregulation
Vascular bed
Endothelial factors
Metabolic autoregulation Tissue

- the balance between local regulatory mechanisms and extrinsic

factors in vivo determines the vascular tone and therefore the blood
flow within the tissue.
Autoregulation of the local blood flow
I. Myogenic autoregulation
-play a role in autoregulation of blood flow to maintain the blood pressure
-Does not plays a role in lung circulation
The smooth muscle of the blood vessels reacts to
the stretching by opening ion channels, which cause
the muscle to depolarize, leading to muscle
contraction. This significantly reduces the volume of
blood flow through the blood vessel, resulting
in vasodilation of the blood vessel due to the ion
channels close; this increases the rate of flow
through the lumen.
 Myogenic autoregulation

Pressure

Diameter

Time
II. Importance of endothelium
The endothelial cell layer

1.5 kg organ

Multiple functions
 Endothelium
Endothelium form a multifunctional
signal-transducing surface that
performs different tasks (vascular tone
regulation, delivery of oxygen, regulation of
permeation of metabolites, etc.).
Endothelium is known to have important
regulatory effects on the cardiovascular
system through the release of vasodilator
and vasoconstrictor factors.
 Functions of the endothelial cell layer

Capillary transport and exchanges between

blood and tissue
Prevention of adherence of platelets,
leucocytes, and monocytes
Regulation of vascular tone
Activation of angiotensin I
Inactivation of noradrenaline, serotonin,
bradykinin
Production of growth factors, i.e. VEGF
Production of factors involved in blood clotting
(factor VIII, plasminogen activators/inhibitors)
Vascular structure
Endothelium Smooth muscle Adventitia
Endothelium-derived vasoactive
substances

Shiogai et al., 2010

 Endothelium-derived vasoconstricting
substances

Endotelin (ET-1, ET-2, ET-3)

Prostaglandin (prostaglandin H2)
Reactive oxygen species
Endothelin family
Factors increasing ET release

Barton, 2008
Endothelin actions
ET-1 and regulation of vascular tone
Endothelium released relaxing substances

Nitric Oxide (NO)

Endothelium
derived
hyperpolarizing
factor (EDHF)
Prostacyclin
(PGI2)

Stankeviius ir kt., Medicina 2003

Discovery of Nitric Oxide (1998)
Endothelium-dependent regulation of vascular
tone

(Furchgott & Zawadzki, Nature 1980)

 Setup for simultaneous measurement of NO and
force
A B

NO
Electrode mN

Force
R
A force

Myograph I NA ACh
K
L NO
I
S
NO (14 pA)

5min
NO sensitive microelectrode = 30 m

Stankeviius ir kt., BJP, 2006

Inhibition of the NO release in Human
endothelium (HUVEC)

A B

Histamine (1 M) Histamine (1 M)

24 nM

7 min ADMA

Stankeviius, 2006
Effect of the removal of endothelium and the inhibition of
NOS in the rat superior mesenteric artery
Control E- Indo
A B C Indo+ADMA Indo+ADMA+OxHb
E+ E- 20

Relaxation (%)
0

20 * *
40

60

80
2 Nm-1 *
100

Acetylcholine (10 M)

D 20.0
17.5
15.0
10 nM

NO (nM)
12.5
10.0
7.5
5.0
5 min 2.5 * * *
ACh (10 M) 0.0

NA (0.5 M) -2.5

Acetylcholine (10 M)
Membrane potential in the endothelial cell

Rat superior mesenteric artery

0
Em(mV)

50

ACh (10 M)
Apamin + ChTx

n=5
10 min
Stankevicius et al., BJP, 2006
 L-Arginine transport sytems:
1. Na+ - dependent
2. Na+ - independent K+ K+

IKCa SKCa
y+
Ca2+
Na+ ER
G
L-Arg IP3
PLC

NOS

K+
NO
BKCa
sGC
cGMP relaxation
GTP
Calcium measurements in HUVEC
 Calcium measurements in HUVEC
Baseline 1 M histamine 1 M Ionomycin 2 mM MnCl

EX340 nm

EX380 nm

EX360 nm
 Endothelial cell transduction in the intact rat mesenteric arteries

ChTx apamin
K+ K+
SKF96365 Ca2+
IKCa SKCa Ach
L-Arg ][
Ca2+
Ca2+ ER
L-Arg G
IP3
PLC

NOS
EDHF
LARGE SMALL
ARTERIES NO ARTERIES
NO K+
BKCa
sGC
cGMP relaxation
GTP
 III. Metabolic autoregulation
Local vasodilation:
pCO2 leads to acidosis in interstitium (H+)
inactivating Ca2+ channels
pO2 increases release of endothelium
derived relaxing factors
K+ concentration leads to membrane
hyperpolarisation
Adenosine acts on A2 receptors decreasing
[Ca2+]I and lowering release of NA from
sympathetic nerves
Coronary Circulation
Coronary circulation depends on:
Blood pressure changes in Aorta
Compression of coronary arteries during
systole
Oxygen demand
The Heart muscle uses 70-80% of Oxygen

The main way to

increase Oxygen
demand
increasing coronary
blood flow!
Regulation of the coronary flow
I. Metabolic vasodilation (overlaps
sympathetic vasoconstriction):
pO2
pCO2
Adenosine A2 receptors [Ca2+]i
K+

II. Sympathetic vasoconstriction:

adrenoreceptors contracts VSMCs
Skms studijuojant

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