Transcript Prezentace aplikace PowerPoint

Regulation of blood pressure
&
Special circulations
Long-term and short-term control of ABP
Short-term
Long-term
Baroreflex
heart
resistence &
compliance
Blood Volume
hypertrophy
Angiotensin II
drinking
Vasopressin
renal excretion
NO
Na-intake
ANP
Endothelin
Sympathetic nervous
system
Ackermann
Blood pressure regulation
vasodilatation
stimulation of
cGMP
vasoconstriction
stimulation of
cAMP
inhibition of
cAMP
Stimulation of
IP3
In smooth muscle, cGMP and cAMP
stimulates Ca2+ pump of the
sarcoplasmic reticulum
Decrease of Ca2+ concentration in
smooth muscle cell
Slower decrease IP3 releases Ca2+
of Ca2+
from the
sarcoplasmic
reticulum
NO
ANP
serotonin
serotonin
adrenaline a2
angiotensin II
adrenaline a1
vasopressin
adenosine A2
histamine H2
adrenaline b2
VIP
Regulation of blood flow
myogenic
metabolic
stretch-activated cation channels cause
vasoconstriction
metabolic products cause vasodilatation
shear
dependent
neural
vasodilatation by NO, which is produced in
vascular endothelium
•sympathetic constrictor nerves in most
tissues
•parasympathetic dilator nerves in some
secretory and spongiform tissues
humoral
•constriction by angiotensin II, epinephrine,
vasopressin, serotonin
•dilatation by ANP, histamine, inflammatory
mediators
Myogenic autoregulation
• Arterioles contracts when they are distended
(brain, kidney, heart)
• Mechanism
– Stretch-activated Na+ and Ca2+ channels of
vascular smooth muscle
– Depolarization of membrane, which then
activates L-type Ca2+ channels
– Muscle contraction
Metabolic regulation
• Adenosine
– Causes vasodilatation, except of kidney and
pulmonary artery
– Activation of adenosine A2A membrane receptor –
elevation of cAMP
• pO2
– Reduction in pO2 increases production of
vasodilator agents (PGI2 and NO)
• pCO2
– Elevated pCO2 leads to elevated H+ in
extracellular fluid – acidosis causes membrane
hyperpolarization (K+) – vasodilatation (except of
lung)
Shear-dependent regulation
• Endothelial cell reacts on many physiological
stimuli with production of several substances
which influence smooth muscle cell
–
–
–
–
Stretching
Shear stress induced by blood flow
Hormonal levels
Substances released from blood elements
(trombocytes, macrofages)
• Synthesis of NO and PGI2 (vasodilators)
Nitric oxide synthesis
• Shear stress and a variety of
receptor-mediated agonists
raise vascular endothelial
[Ca++] and cause the Ca++calmodulin complex to
activate endothelial nitric
oxide synthase (eNOS).
• NO is produced from the
amino acid L-arginine.
• NO is a gas and diffuses into
adjacent VSM where it
activates soluble guanylate
cyclase, produces cGMP and
causes vasodilatation
Ackermann
Neural regulation
• Sympathetic nerves
– Constrictor nerves – mediator noradrenaline - a1
adrenoreceptors
– Elevates Ca++ through phospholipase C pathway (IP3)
• Parasympathetic nerves
– In tissues which need sudden increase in blood flow
(salivary gland, external genitalia)
– Mediator acetylcholine has indirect effect
• inhibition of noradrenalin release
• production of NO
Hormonal regulation
• Renin-angiotensin, vasopressin, ANP
• Adrenaline (epinephrine)
– Higher affinity for b-adrenoreceptors (heart,
splanchnic area, skeletal muscle) – vasodilatation
– Lesser affinity for a-adrenoreceptors
(vasoconstriction)
• Serotonin
– released from platelets during clotting reaction,
elevated Ca2+ leads to vasoconstriction
• Histamine
– Vasodilatation by means of NO production
Renin-angiotensin II-aldosteron system
• Regulates ABP by regulating blood volume
• A decrease in ABP – decrease in renal
perfusion pressure
– Mechanoreceptors in afferent arterioles
– Juxtaglomerular cells secret renin (proteolytic
enzyme)
– In plazma, renin catalyzes the conversion of
angiotensinogen to angiotensin I (a decapeptide)
– In lungs, angiotensin I is converted to angiotensin II
(catalyzed by angiotensin converting enzyme (ACE)
(an octapeptide)
Role of angiotensin II
• In the zona glomerulosa cells of adrenal
cortex stimulates production of aldosterone
– In renal distal tubule and collecting duct increases
Na+ reabsorption – increases ECF volume and
blood volume
• In arterioles angiotensin II causes
vasoconstriction – increase in TPR
• In the renal proximal tubule stimulates Na+-H+
exchange – increase in ECF volume
• In the CNS stimulates thirst an drinking
behavior
Antidiuretic hormone
• Secreted by the posterior lobe of the pitiutary
gland after
– increased osmolarity
– decreased ABP (e.g. hemorrhage), atrial volume
receptors are stimulated
• Regulates body fluid osmolarity
• 2 types of receptors:
– V1: in vascular smooth muscles – cause
vasoconstriction of arterioles, increase TRP
– V2: in renal collecting ducts are involved in water
reabsorption, maintain osmolarity
Atrial natriuretic peptide
• ANP is secreted by the atria in response
to increase in ECF volume and atrial
pressure
• Mechanism of action:
– Relaxation of vascular smooth muscle –
vasodilatation, decrease TPR
– In the kidney – increased Na+ and water
excretion = decrease ECFV and ABP
Chemoreceptors in carotid
and aorctic bodies
• Chemoreceptors – high rates of O2 consumption,
sensitive to decrease of pO2
• Afferentatiton to the medullary cardiovascular
centers – increase in sympathetic outflow to the
heart and blood vessels – increase ABP and
delivery of O2
• Chemoreceptors are also sensitive to pCO2 and pH,
but the reflexes are smaller compared with changes
in pO2
Cerebral chemoreceptors
• Chemoreceptors in the medulla are most sensitive
to pCO2 and pH and less sensitive to pO2
• Reflex during decreased cerebral blood flow:
– increase in pCO2 and decrease in pH activates
chemoreceptors
– Increase in both sympathetic and parasympathetic
outflow
– Increased contractility, increased TPR but decreased
heart rate
– Intense arteriolar vasoconstriction redirects blood flow
to the brain
Baroreceptors
• Baroreceptors are mechanoreceptors –
sensitive to changes in pressure or stretch
• located within the walls of the carotid sinus and
the aorctic arch
– Carotid sinus – (changes in arterial pressure) afferent IX. cranial nerve n. glossopharyngeus
– Aorctic arch – (increase in arterial pressure) X.
cranial nerve n. vagus
– cardiovascular vasomotor centers in the brain stem
• Baroreflex - fast regulation – via changes in he
output of sympathetic and parasympathetic NS
Brain stem cardiovascular centers
• Localized in reticular formation of medulla and
lower 1/3 of the pons
• Information from IX. and X. nerves is integrated in
nucleus tractus solitarius and redirected to
• Cardiac decelerator center – PNS – n. vagus –
SA node – decrease heart rate
• Cardiac accelerator center – SNS – SA node
(increase heart rate, conduction velocity through
the AV node, contractility)
• Vasoconstrictor center – SNS – vasoconstriction
of arterioles and venules
Midbrain regions of CV control
Rostral
ventrolateral
medulla
Cardiac accelerator
center
Vasoconstrictor center
Area postrema
Nucleus tractus
solitarius
Nucleus ambiguous
Cardiac decelerator center
Caudal ventrolateral
Medulla
Fibers from this neurons project
to the vasoconstrictor area and
inhibit it
Sympathetic nerve activity and arterial
pressure
•Decreasing blood pressure
is followed with increasing
sympathetic nerve activity
•Vasoconstriction increases
blood pressure
Regulation of mean arterial pressure (ABP)
ABP (mmHg) = cardiac output (ml/min) x total
peripheral resistance (mmHg/ml/min)
CO = stroke volume (ml) x heart rate (c/min)
• Cardiac output and TPR are not independent
variables
– when TRP increases, CO compensatory decreases
• Regulation of ABP – comparing ABP with the
set-point value (100 mm Hg)
increase
in ABP
activation of
baroreceptors
increase firing
rate in IX., X.
cardiac decelerator center
decrease
of heart rate
decrease
of heart rate
contractility
vasodilatation
increased
parasymp.
outflow
decreased
sympathetic
outflow
increased
activity
of NA
stimulation
of NTS
decreased
activity
CAC
decreased
activity
VC
CAC - cardiac accelerator center, VC – vasoconstrictor center
Estimation of baroreceptor sensitivity
Index of baroreceptor sensitivity = PI/SBP (ms/mmHg)
Association between broreceptor sensitivity
and hypercholesterolemia
Persons with higher level
of LDL cholesterol have
lower baroreceptor
sensitivity
Koskinen et al. 1995
Changes in posture from supine position to
standing
• Mechanism of orthostatic hypotension
– Blood pools in the veins of lower extremities
– Venous return to the heart decreases, cardiac
output decreases (Frank-Starling law)
– Mean arterial pressure decreases
– Decreased activation of baroreceptors
– Increased sympathetic outflow to the heart
and blood vessels and decreased
parasympathetic outflow
Special circulations
• Different organs have
– Differences in vascular resistance
– Differences in metabolic demands
• Local control (intrinsic)
• Hormonal control (extrinsic)
Cerebral circulation
• 15 % of cardiac output
• Is controlled by local metabolites
–
–
–
–
–
pCO2 (H+) is the most important vasodilator
CO2 diffuses to vascular cells, forms H2CO3 (H+)
Intracellular H+causes vasodilatation
Increase in blood flow, removal of excess CO2
Decrease in pO2 increases cerebral blood flow
• Many vasoactive substances do not affect cerebral
circulation, do not cross the blood-brain barrier
Coronary circulation
• 5 % of cardiac output
• Local metabolic factors
– Hypoxia: increase in myocardial contractility –
increased O2 consumption – local hypoxia
– Hypoxia causes vasodilatation of the coronary
arterioles – compensatory increase in blood flow
and O2 delivery
– Adenosine (from ATP) causes vasodilatation
• Mechanical compression of the blood vessels
during systole in the cardiac cycle – brief
period of occlusion and reduction of blood flow
Pulmonary circulation
• 100% of cardiac output
• Lower pressure and low resistance
• Controlled by local metabolites, primarily by
pO2 (bellow 70 mm Hg)
• Opposite effect than in other tissue – hypoxia
causes vasoconstriction
– Mechanism – inhibition of NO production in
endothelial cells of blood vessel walls
– Redistribution of blood from poorly ventilated
areas to well-ventilated areas
Renal circulation
• 25 % of cardiac output
• Renal blood flow is autoregulated
– Constant blood flow even when renal perfusion
pressure changes (80-200 mmHg)
– Renal autoregulation is independent of sympathetic
innervation (transplanted kidney)
– Angiotensin II – vasoconstrictor for both afferent and
efferent arterioles, but efferent arteriole is more
sensitive
– Prostaglandins (E2, I2 – produced locally) –
vasodilatation of both arterioles
Skeletal muscle circulation
• 25 % of cardiac output
• Sympathetic innervation
– At rest: activation of a1 (noradrenaline) receptors
causes vasoconstriction, increased resistance and
decreased blood flow
– Activation of b2 (adrenaline) receptors causes
vasodilatation
• Local metabolites
– During exercise: local vasodilator – lactate,
adenosine, K+
Skin circulation
• 5 % of cardiac output
• Dense sympathetic innervation – regulates
blood flow for regulation of body temperature
– Increase core body temperature – decrease
sympathetic tone to the smooth muscle sphincters
controlling A-V anastomoses - increase skin blood
flow
• Arteriovenous anastomoses – permit bypass
of the capillary vessels
circulation
local metabolic
control
sympathetic
control
mechanical
effects
coronary
hypoxia
adenosine
least important
compression
during systola
cerebral
CO2
H+
least important
increased
intracranial
pressure
decreases CBF
skeletal
muscle
during exercise
lactate
K+
adenosine
at rest
muscular
a vasoconstriction activity
compresses
b vasodilatation
blood vessels
skin
-
a vasoconstriction -
pulmonary
hypoxia
vasoconstricts
least important
renal
myogenic
least important
lung inflation