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MF-local Circulation 2016 PDF
MF-local Circulation 2016 PDF
MF-local Circulation 2016 PDF
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.
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.
Pulmonary
Arteries and Vessels 12%
arterioles 15%
Heart 8%
Capillaries 5%
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
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
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
Barton, 2008
Endothelin actions
ET-1 and regulation of vascular tone
Endothelium released relaxing substances
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
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
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
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