Essentials of Blood Pressure Regulation in Hypertension

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Essentials of Blood Pressure Regulation in
Hypertension
Dr. Thomas Abraham PHAR 417 Fall 2005
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Blood Pressure Regulation in Hypertension
Population dynamics of Hypertension and related
pathologies

• 60,000,000 Americans have one or more forms of
  cardiovascular disease (2002)
• Hypertension is prevalent in about 35 of the
  adult population (50,000,000).
• Coronary heart disease 12, 600, 000
• Stroke 4, 600, 000

• Cardiovascular disease claimed almost 800 000
  lives in 1999 nearly twice as many as cancer, 10
  times as much as accidents and about 60 times as
  much as AIDS (1997)
• In 2002 Cardiovascular disease is estimated to
  cost the nation 330 billion in healthcare costs.
• As the population ages these statistics are
  expected to increase.

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Blood Pressure Regulation in Hypertension

• Blood pressure influenced by
• 1. Peripheral vascular resistance which in turn
  is controlled by
• - vessel diameter vasoconstriction/vasodilation
  
• - blood viscosity changes in hematocrit,
  osmolarity
• - total vessel length effects of fat tissue
  and weight loss.
• Vessel elasticity
• - Stiffening of arteries due to arteriosclerosis
  decreases vessel compliance and lumen pressure
  during pulsatile blood flow.
• - Decreases with age.
• Blood volume
• - Increases in volume cause sustained increases
  in systemic pressure.
• - Short-term changes in volume produced by
  decreased venous pooling
• - Long-term changes controlled by the kidneys.
• Cardiac Output
• - amount of blood ejected by the heart per cycle
  maintains the pressure in the circulation.

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Blood Pressure Regulation in Hypertension
Short-term Blood Pressure Regulation I. By
changes in vessel (arteriolar) diameter
Largest systemic pressure drop occurs in the
arteriolar beds thus this is the region with the
greatest resistance to blood flow. Changing the
lumen diameter in these vessels will also
influence the systemic blood pressure the
greatest. Thick layer of muscular tunica media
in arteries and arterioles allows for rapid
change in vessel lumen diameter in response to
sympathetic nerve stimulation or blood-borne
hormone.
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Blood Pressure Regulation in Hypertension

• Autonomic control of blood pressure
• Most arteries and some veins receive nerve
  inputs from postganglionic sympathetic neurons,
  with arteries and arterioles being more densely
  innervated.
•  
• Cardiovascular centers in the medulla oblongata
  initiate tonic sympathetic discharge that is
  transmitted down the spinal cord, via the
  presynaptic fibers and chain ganglia to the
  vasculature. Thus release of norepinephrine
  within the wall of arteries is responsible for
  activating a1-adrenoceptors to cause
  vasoconstriction.

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Blood Pressure Regulation in Hypertension

• Autonomic Regulation of BP
• Epinephrine (and some NE) released from
  adrenal medulla during sympathetic activation
  thought to activate the a2-adrenoceptor, which is
  more densely localized on the lumenal side of the
  smooth muscle layer.
• Tissue metabolites (lactic acid,
  prostaglandins) and increasing PCO2 (decreasing
  PO2) can cause vasodilation of arterioles and
  venules to increase tissue blood flow.

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Blood Pressure Regulation in Hypertension
II. By changes in heart rate and contractility
Mean Arterial Pressure Total Peripheral
Resistance X Cardiac Output
Influenced by vessel diameter
Influenced by cardiac function
Changes in TPR or CO or both can influence the
mean blood pressure in an individual. Generally
sympathetic nervous system activation results in
alteration of both parameters while various drugs
may have selective effects on one or the other.
(Pulse Pressure)
MBP DBP
3
Pulse Pressure Systolic Pressure Diastolic
Pressure
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Blood Pressure Regulation in Hypertension
Cardiac Output Heart Rate X Stroke Volume
Stroke volume is related to myocardial
contractility therefore increasing contractile
force of the heart increases stroke
volume. Both stroke volume and heart rate
influence the amount of blood the heart delivers
per cardiac cycle to the circulatory system
(cardiac output).    b-adrenoceptor agonists
directly increase the rate and contractility of
the heart to influence the CO of the heart.
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Blood Pressure Regulation in Hypertension
Baroreceptor control of short-term Blood Pressure

• Baroreceptors are stretch receptors found in
  the walls of the carotid sinus and the aortic
  arch that detect changes in arterial pressure.
•  
•  
• Increases in blood pressure cause distention
  of the baroreceptors leading to increased rate of
  firing of afferent sensory nerves that eventually
  inhibit the tonic firing of the sympathetic motor
  center in the medulla.

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Blood Pressure Regulation in Hypertension
Autonomic Reflex Arc
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Blood Pressure Regulation in Hypertension
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Blood Pressure Regulation in Hypertension
The baroreceptor reflex is concerned with
maintenance of the mean blood pressure. Drugs
that cause increases in MBP initiate the reflex
to bring down the pressure. The opposite would
occur if vasodilatory drugs were administered or
if MBP suddenly fell.
Decrease in heart rate may be due to activation
of baroreceptors leading to increased PNS
activity and decreased SNS activity. Decreased
baroreceptor stimulation with ISO may lead to
increased SNS activity to increase HR and force.
BP
Phenylephrine 10 ug/kg
Force
Prazosin 1 ug/kg
HR
3
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Blood Pressure Regulation in Hypertension
Long-term Blood Pressure Regulation Ø     
Mainly achieved by the regulation of blood volume
by the kidneys.   Ø      The Renin-Angiotensin-A
ldosterone axis for volume regulation   o      
Changes in blood volume due to sustained blood
loss are detected by the Macula Densa cells of
the kidneys as a decrease in Na in the
glomerular filtrate.     o       Juxtaglomerular
cells of the kidneys are stimulated to release
renin into the blood which converts
angiotensinogen to angiotensin I.
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Blood Pressure Regulation in Hypertension

• Renin-Angiotensin-Aldosterone axis
• o       Angiotensin I is converted to
  angiotensin II by angiotensin- converting enzyme
  (ACE) found on endothelial cells.
•   o       Angiotensin II is a potent
  vasoconstrictor that helps maintain the falling
  blood pressure.
•   o       Angiotensin II also releases
  aldosterone from the adrenal cortex, which
  causes increased Na and water reabsorption from
  the distal convoluted and collecting tubules.

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Blood Pressure Regulation in Hypertension
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Blood Pressure Regulation in Hypertension
Ø      Anti-diuretic hormone (Vasopressin) and
control of blood volume o       Increases in
blood osmolarity are detected by the pituitary to
cause release of ADH into the blood.     o      
ADH is a vasoconstrictor that helps maintain
blood pressure.     o       ADH increases water
reabsorption in the DCT and collecting ducts of
the kidneys.   o       ADH stimulates the thirst
centers of the hypothalamus to increase water
intake.  
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Blood Pressure Regulation in Hypertension

• Etiology and Pathology of Hypertension
• Less than 15 of hypertension cases have any
  identifiable causes (secondary hypertension)
  aortic coarctation, renal artery constriction,
  Cushings syndrome, pheochromocytoma, primary
  aldosteronism.
•  
• Common findings in essential hypertension (of
  unknown cause) include vascular smooth muscle
  hypertrophy, cardiac ventricular hypertrophy,
  decreased vessel compliance (stiffening) and
  increased arterial tone.

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Blood Pressure Regulation in Hypertension

• Etiology and Pathology of Hypertension
• Risk factors associated with hypertension
  heredity, race, gender, age, high salt diet,
  obesity, smoking and physical inactivity.
•  
•  
• Untreated hypertension can result in
  atherosclerosis, stroke, myocardial infraction,
  cardiac hypertrophy, arrhythmias, congestive
  heart failure, renal failure.
•   
•  
• Blood pressure consistently above 150/95
  requires pharmacological intervention while the
  presence of one or more risk factors may demand
  therapy at a lower threshold.