Cardiovascular Pharmacology

Review of Cardiovascular Form

and Function

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 contraction
Height of ventricle discharge pressure

Integrity of vasculature
Presence of blockage
Muscular tone/structural integrity
Pressure drop needed to move blood to and through
capillary beds

Blood volume/composition
Water, electrolyte, iron balances
Lipid and protein composition

Major Cardiovascular Pathologies

Requiring Pharmacological Intervention
Hypertension
Arrhythmia
Heart failure
Reduced vascular blood flow

I. Background to Hypertension Regulation of Blood Pressure

Arterial blood pressure due to combination
of cardiac output (CO) and total peripheral
resistance (TPR)
CO regulated by heart rate and stroke
volume (CO = HR x SV)
TPR function of

Viscosity of blood (hematocrit)

Length of blood vessels
Blood vessel luminal diameter (especially
precapillary arterioles)

Cardiac Output
Heart rate

Function of

sympathetic, vagal nervous activity

Neuro-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, 2 receptors)

Vascular volume depends on
Intake of fluids (thirst)
Output of fluids (urine, sweat, etc)
Distribution of fluids (Starlings law)

Myocardial contractility (MC proportional to sympathetic

tone [1 receptors])

Characteristics of some adrenoceptors

(sympathetic nerves)
Tissues
receptors

and effects
1

constrict

constrict/
dilate

Smooth
muscle
Arteries/
veins

dilate

Skeletal
muscle

dilate

Heart
Rate

(increase)

Force of
contraction

increase

Beat-to-Beat Modulation of Blood

Pressure
Controlled by baroreceptor reflex arch
Baroreceptors located in aortic arch
Increased stretching due to higher aortic arch
pressure increased vagal nerve activity
decreased heart rate decreased cardiac
output decreased blood pressure
Fast acting

Autonomic Regulation of Blood Pressure

Coordinates and integrates all
regulators of cardiovascular function
Can regulate both cardiac output and
blood vessel size via sympathetic and
parasympathetic innervation of
cardiovascular end-organs (heart,
vasculature, kidneys, adrenal glands,
etc)

Autonomic Regulation of the Heart

Heart Rate
Parasympathetic input via vagus nerve
causes decrease in HR (dominates)
Sympathetic input to sino-atrial node
causes increase in HR (usually minor)

Heart contractility
Increased by sympathetic activity
causing release of epinephrine,
norepinephrine from adrenal gland

II. Background to Arrhythmia Rhythm of the Heart

Human heart is fourchambered
Chambers need to contract
sequentially (atria, then
ventricles) and in
synchronicity
Also need relaxation
between contractions to
allow refilling of chambers
Above controlled
electrically (Purkinje fibers
allow rapid, organized
spread of activation)

Regulation of Heart Rate

Primarily accomplished by sinoatrial node (SA)
Located on right atrium
Receives autonomic input
When stimulated, SA signals atrial contractile fibers
atria depolarization and contraction (primes
ventricles with blood)

Depolarization picked up by atrioventricular

node (AV node) depolarizes ventricles
blood discharged to pulmonary artery and
dorsal aorta eventually rest of body

Sequential Discharge of SA and AV nodes

III. Background to Congestive Heart Failure

Maintenance
ofneeded
Normal
Heartperfuse
Function
Normal cardiac output
to adequately
peripheral 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 in
venous 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 inadequate

perfusion and development of the syndrome of heart failure

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

Quantification of Total Peripheral Resistance

TPR =

_L _ for sum of all blood vessels

r4
(Poiseuilles equation)

Where

r = radius of blood vessel

L = length of blood vessel
= viscosity of blood (function of
hematocrit) hematocrit =

Therefore: change in blood vessel radius has

greatest effect on TPR
Note: 70% of TPR produced/controlled by
arterioles target of drug treatment

Relationship between blood flow

and radius of a blood vessel

0.063

0.5

Relationship between blood pressure,

velocity and total area of vasculature

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 I
Angiotensin II in lung

Angiotensin II:
Actions:
Intense vasoconstriction increase TPR
Causes release of Aldosterone from adrenal gland promotes Na+ and
water 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 pressure

back up to normal set-point

Autonomic regulation
of the vasculature
Increased sympathetic activity
reduction in blood vessel opening
(caliber) increase in vascular
resistance etc. etc increase
blood pressure

Stop talking now and

let them go!
Im outta
here!