Local Control of Blood Flow

Reading

• Klabunde, Cardiovascular Physiology

Concepts
– Chapter 7 (Organ Blood Flow) pages 141-151.
Regulation of Peripheral Blood Flow

• Dual Control
– Extrinsic
• Primarily by the nervous system
• Humorally also

– Intrinsic (Locally in the tissues)

• Controlled by the conditions in the immediate
vicinity of the blood vessels
Regulation of Peripheral Blood Flow
Pharmacologic Stimuli that Cause Contraction
or Relaxation of Vascular Smooth Muscle

• Catecholamines • Histamine
– Epinephrine • Adenosine
– Norepinephrine • Nitric Oxide (NO)
– Dopamine
• Carbon Dioxide
• Endothelin
• Potassium
• Serotonin
• Hydrogen Ion
• Angiotensin II
• Prostaglandins
• Vasopressin
• Acetylcholine
• Bradykinin
Intrinsic Control of
Local Blood Flow:

Metabolic Factors
Tissue Metabolic Activity Is the Main Factor in
Acute Control of Local Blood Flow

• One of the most fundamental principles of

circulatory function is the ability of each tissue to
control its own local blood flow in proportion to
its metabolic needs

• Metabolic Mechanism
– Any intervention that results in an inadequate oxygen
(nutrient) supply for the metabolic requirements of the
tissues results in the formation of vasodilator
substances which increase blood flow to the tissues.
Acute Local Feedback Control
of Blood Flow

Metarteriole

Precapillary Relaxation of smooth muscle

Sphincter

Lack of oxygen?
Capillary Formation of vasodilators?
Combination of both??

Increased Blood Flow

 Metabolic Mechanisms
• Hypoxia

• Tissue metabolites and ions

– Adenosine
– Potassium ions
– Carbon dioxide
– Hydrogen ion
– Lactic acid
– Inorganic phosphate
 Examples of Metabolic Control
of Local Bloodflow
• Active Hyperemia

• Reactive Hyperemia
Active Hyperemia
Reactive Hyperemia
 Reactive Hyperemia
• Within limits the peak blood flow and the
duration of the of the reactive hyperemia
are proportional to the duration of the
occlusion
Intrinsic Control of
Local Blood Flow:

Autoregulation
 Autoregulation
• Intrinsic ability of an organ to maintain a
constant blood flow despite changes in
perfusion pressure

• Possible explanations for Autoregulation:

– Myogenic Mechanism
– Metabolic Mechanism
Ohm’s Law

Pa  Pv
Q
R
Cerebral Autoregulation
 Autoregulation

No Autoregulation
Resistance
Autoregulation
No Autoregulation

Flow

Pressure

Time
 Theories to Explain Autoregulation:
Myogenic Mechanism

• When the lumen of a blood vessel is suddenly

expanded, the smooth muscles respond by contracting
in order to restore the vessel diameter and resistance.
The converse is also true.

• Vascular smooth muscle cells depolarize when

stretched.

• Proposed mechanism is stretch of vascular smooth

muscle causes activation of membrane calcium
channels.
Theories to Explain Autoregulation:
Myogenic Mechanism

P1 ↑P ↑P
Q1 ↑Q Q1
Theories to Explain Autoregulation:
Metabolic Mechanism

• When the pressure increases to a tissue, the

flow increases, and excess oxygen and nutrients
are provided to the tissues. These excess
nutrients cause the blood vessels to constrict
and the flow to return nearly to normal despite
the increased pressure.
Intrinsic Control of
Local Blood Flow:

Endothelial Factors
 The endothelium plays an active role in
regulating the microcirculation
• Endothelium is a source of substances that elicit
contraction or relaxation of the vascular smooth
muscle

• Vasoactive substances released from

endothelium:
– Nitric Oxide (NO)
• Endothelium-derived relaxing factor
– Prostacyclin
– Endothelin
– Endothelial-derived hyperpolarizing factor (EDHF)
Nitric Oxide
 Nitric Oxide
• Generated from amino acid L-arginine

• Generated from NO synthase

• Increases GMP concentration which produces relaxation

by decreasing cytosolic free calcium

• Very short half-life (6 seconds)

– Due to rapid oxidation to nitrite and nitrate
– Also due to binding by substances such as hemoglobin

• NO is a gas and must be delivered by an inhaled

delivery system
 Nitric Oxide

• NO production is stimulated by:

– Shearing forces acting on the endothelium

– Acetylcholine
– Bradykinin
– Histamine
– Insulin
– Substance P
 Nitric Oxide

• Important functions in cardiovascular system:

– Vasodilation
– Inhibition of vasoconstrictor influences
– Inhibition of platelet adhesion to the vascular
endothelium
– Inhibition of leukocyte adhesion to the vascular
endothelium
– Antiproliferative
– Free radical scavenger
 Nitric Oxide

Systemic Effects:

• Pulmonary vasodilation
– Decreased pulmonary vascular resistance
– Decreased pulmonary artery pressure
– Pulmonary vasodilation decreases right ventricular afterload and
improves right ventricular performance

• Increased arterial oxygen tension

– Inhaled nitric oxide is delivered only to ventilated alveoli.
• This improves V/Q relations by vasodilating capillaries and
improving blood flow to areas participating in gas exchange.
 Nitric Oxide

NO
Rapid binding of NO by
NO Hgb limits hemodynamic
effects of NO
NO
Shunt
NO
Reduced
NO NO NO -
NO NO Hgb
NO
NO

Nitric oxide-induced pulmonary vasodilation

allows blood to preferentially flow by
ventilated lung units
Prostacyclin
 Prostacyclin

• Prostacyclin synthase in endothelial cells

acts on cyclo-endoperoxide products to
form Prostacyclin (PGI2)

• Prostacyclin (PGI2)
– Strong vasodilator
– Inhibits platelet adhesion to the vascular
endothelium
Endothelin
 Endothelin
• Synthesized by endothelium

• Potent vasoconstrictor
• Other actions:
– Increased aldosterone secretion
– Increased cardiac inotropy and chronotropy
– Decreased renal blood flow and GFR
– Releases atrial natriuretic peptide
– In failing heart, contributes to calcium
overload and hypertrophy
 Endothelin

• Implicated in the pathogenesis of:

– Hypertension
– Vasospasm
– Heart failure
– Pulmonary hypertension
 When Damage to Endothelium Occurs

• Damage to endothelial cells will lead to:

– Decreased Nitric Oxide and Prostacyclin
production
– Increased Endothelin production

• This will lead to:

– Vasoconstriction
– Vasospasm
– Thrombosis
THE END