Download - Cardiovascular Pharmacology.ppt
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Cardiovascular Pharmacology
Review of Cardiovascular Form
and Function
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Introduction and Background
Cardiovascular disease is the major cause
of death in the US (>50% of all deaths)Cardiovascular function based on Cardiac pumping ability
Pace-making electrical signals
Force of contractionHeight of ventricle discharge pressure
Integrity of vasculaturePresence of blockage
Muscular tone/structural integrity
Pressure drop needed to move blood to and throughcapillary beds
Blood volume/compositionWater, electrolyte, iron balances
Lipid and protein composition
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I. Background to Hypertension -
Regulation of Blood Pressure
Arterial blood pressure due to combinationof cardiac output (CO) and total peripheralresistance (TPR)
CO regulated by heart rate and strokevolume (CO = HR x SV)
TPR function of
Viscosity of blood (hematocrit)
Length of blood vessels
Blood vessel luminal diameter (especiallyprecapillary arterioles)
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Cardiac Output
Heart rate
Function ofsympathetic, vagal nervous activityNeuro-hormonal substances
1 angiotensin II 2 vasopression (anti-diuretic hormone = ADH)
Stroke volume Function of
Venous return (function of venous tone [contractile state]and circulating blood (vascular) volume)
Venous tone function of sympathetic activity (1, 2receptors)
Vascular volume depends onIntake of fluids (thirst)Output of fluids (urine, sweat, etc)Distribution of fluids (Starlings law)
Myocardial contractility (MC proportional to sympathetic
tone [1 receptors])
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Characteristics of some adrenoceptors
(sympathetic nerves)
1 2 1 2
Smoothmuscle
Arteries/
veins
constrict constrict/
dilate
dilate
Skeletal
muscle
dilate
Heart
Rate (increase)
Force of
contraction
increase
Tissues
and effects receptors
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Beat-to-Beat Modulation of Blood
Pressure
Controlled by baroreceptor reflex arch
Baroreceptors located in aortic arch
Increased stretching due to higher aortic archpressure increased vagal nerve activity decreased heart rate decreased cardiac
output decreased blood pressure
Fast acting
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Autonomic Regulation of Blood Pressure
Coordinates and integrates allregulators of cardiovascular function
Can regulate both cardiac output andblood vessel size via sympatheticand parasympathetic innervation of
cardiovascular end-organs (heart,vasculature, kidneys, adrenal glands,etc)
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Autonomic Regulation of the Heart
Heart RateParasympathetic input via vagus nerve
causes decrease in HR (dominates)
Sympathetic input to sino-atrial nodecauses increase in HR (usually minor)
Heart contractility Increased by sympathetic activity
causing release of epinephrine,norepinephrine from adrenal gland
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II. Background to Arrhythmia -
Rhythm of the Heart
Human heart is four-chambered
Chambers need to contractsequentially (atria, then
ventricles) and insynchronicity
Also need relaxationbetween contractions to
allow refilling of chambers
Above controlledelectrically (Purkinje fibersallow rapid, organizedspread of activation)
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Regulation of Heart Rate
Primarily accomplished by sinoatrial node (SA)
Located on right atrium
Receives autonomic input
When stimulated, SA signals atrial contractile fibersatria depolarization and contraction (primes
ventricles with blood)
Depolarization picked up by atrioventricular
node (AV node) depolarizes ventriclesblood discharged to pulmonary artery and
dorsal aorta eventually rest of body
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III. Background to Congestive Heart Failure
Maintenance of Normal Heart FunctionNormal cardiac output needed to adequately perfuseperipheral organs Provide O2, nutrients, etc Remove CO2, metabolic wastes, etc Maintain fluid flow from capillaries into interstitium and back
into venous system
if flow reduced or pressure increased invenous system build up of interstitial fluid = edema
Because CO is a function of Heart Rate determined by pacemaker cells in the sinoatrial
node Stroke volume determined by fill rate and contractile force Atrial/ventricular/valvular coordination
Any negative change on above can lead to inadequateperfusion and development of the syndrome of heart failure
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IV. Background to Reduced Vascular Blood
Flow: Blood Vessel Anatomy and Function
Arterial blood vessels Smooth muscle (slow, steady contraction) elastic tissue (stretch on systole, recoil on diastole) Contain about 10% of blood volume Arterioles have sphincters which regulate 70% of blood pressure
Venous blood vessels Highly distensible, some contractility Contain over 50% of blood volume
Capillaries Tiny but contain greatest cross-sectional area to allow high exchange
rate Contain precapillary sphincters to regulate blood flow 5% of blood volume
All vasculature under ANS and humeral control
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Quantification of Total Peripheral Resistance
TPR = _L _ for sum of all blood vessels
r4 (Poiseuilles equation)
Where r = radius of blood vesselL = length of blood vessel= viscosity of blood (function of
hematocrit) hematocrit =
Therefore: change in blood vessel radius hasgreatest effect on TPR
Note: 70% of TPR produced/controlled byarterioles target of drug treatment
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Relationship between blood flow
and radius of a blood vessel
0.5
0.063
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Relationship between blood pressure,
velocity and total area of vasculature
H l R l ti f Bl d P
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Humeral Regulation of Blood Pressure:
Renin-Angiotensin-Aldosterone System
Renin:secreted by the kidney in response to reduced blood pressure
or blood volume
Angiotensin:Renin converts Angiotensinogen Angiotensin I
Angiotensin Converting-Enzyme(ACE): converts Angiotensin IAngiotensin II in lung
Angiotensin II: Actions:
Intense vasoconstriction increase TPRCauses release of Aldosterone from adrenal gland promotes Na+ andwater reabsorption in kidney cause increased blood volume.
Regulatory negative feedback on the release of Renin.CNS: Stimulate thirst in hypothalamus, stimulate sympathetic outflow.
- All above designed to bring arterial blood pressureback up to normal set-point
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Autonomic regulation
of the vasculature
Increased sympathetic activity
reduction in blood vessel opening(caliber) increase in vascular
resistance etc. etc increaseblood pressure
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Stop talking now and
let them go!
Im outtahere!