Dla: Local Control Of Blood Flow After Lecture 11

Question 1

Define autoregulation of blood flow.

Distinguish between short-term and long-term autoregulatory responses and the mechanisms responsible for each

Answer 1

-An organs metabolic need has a direct relationship with it’s blood flow.

Question 2

Describe how the theory of metabolic regulation of blood flow accounts for active
hyperemia and reactive hyperemia

Answer 2

1) Metabolic (Active, Functional) Hyperemia
- Increases blood flow (increase in vasodillator metabolites) = increase blood flow in skeletal and cardiac muscles

2) Reactive (Post – Ischemic) Hyperemia
-Temporary occlusion of
a blood vessel
-Build up of metabolites
downstream of the occlusion
Vasodilation downstream
-Increases blood flow

Question 3

What’s the relationship between MAP and blood flow?

Describe the contribution of myogenic tone to blood flow regulation.

Answer 3

-MAP and blood flow have a direct relationship, BUT between 60/80-160mmHG no increase in blood flow

Myogenic response:
-Autoregulates blood flow by stretching blood vessel walls and contracting smooth muscle of arterioles
(Ex: cerebral and renal arterioles)

• Vasodilation –> increases flow
• Vasocon. –> decreases flow

Question 4

Identify the role of PaO2, PCO2, pH, adenosine, and K+
in the metabolic control of
blood flow to specific tissues.

Answer 4

-All are metabolic vasodilators responsible for Active and Reactive Hyperemia

PaO2 --> tissues, but constricts lungs
PCO2 --> Cerebral
pH (H+) --> Cerebral
Adenosine --> skeletal, cardiac, renal
K+ --> Skeletal muscle, brain

Question 5

Describe the function and pathway of the synthetic pathway for nitric oxide (EDRF)

Answer 5

• Intrinsic control of blood flow
• Nitric Oxide (EDRF) = vasodilator (Ex: exercise, erection, inflammation)

Pathway:

1) Guanylyl cyclase stimulate
- -> increase cGMP –> Vasodil

Both NO (EDRF) and
prostacyclin limit spread of
platelet aggregation and prevent uncontrolled vascular
thrombosis (Clots)

Question 6

Extrinsic Control of blood flow

Answer 6

-Sympathetic activity → Vasoconstriction

• Parasympathetic activity:
• Release Ach which binds to muscarinic receptors→ Increase NO → Vasodilation

Question 7

Hormonal control of blood flow

Epinephrine and norepinephrine

Answer 7

Epinephrine:

• Can cause BOTH vasodil. and vasocon. (Depends on [ ] )
• Normal [ ]=b2 bound-> vasodil.
• High [ ]=A1 bound-> vasocon.

Norepinephrine:

• Vasoconstricts
• Acts on A1 and B1 receptors
• FYI: HR will decrease bc baroreceptors

Question 8

Nitric Oxide and Inflammation and endotoxin shock

Answer 8

-Cause = activation of inducible NOS

• Inflammatory response: bradykinin, substance P,
thrombin activate both endothelial NOS (eNOS) and
inducible NOS (iNOS).

• Bacterial endotoxins: stimulate monocytes and
macrophages release of interferon-gamma- a potent
stimulator of iNOS
-RISK OF HYPOTENSION

Question 9

Endothelin (ET-1) function and related pathologies

Answer 9

• Intrinsic control of blood flow
• Vasoconstrictor

Pathologies:

1) Hypoxia
2) Preeclampsia
3) Cardiac failure
4) Strokes
5) Migranes

Question 10

Nitric Oxide and Smooth muscle relaxation

Answer 10

-Intrinsic control of blood flow

Ligand binds –> NO generated via NO synthase activity on L-arginine –> NO diffuses to vascular SM cell –> Increase cGMP =

1) decrease ca2+ [}
2) Relaxation of vascular SM
3) Vasodilation

Question 11

Nitric Oxide and Inflammation and endotoxin shock

Answer 11

• Intrinsic control of blood flow
• Cause = activation of inducible NOS

• Inflammatory response: bradykinin, substance P,
thrombin activate both endothelial NOS (eNOS) and
inducible NOS (iNOS).

• Bacterial endotoxins: stimulate monocytes and
macrophages release of interferon-gamma- a potent
stimulator of iNOS
-RISK OF HYPOTENSION

Question 12

Nitric Oxide and Angina Treatment

Answer 12

-Angina pectoris- poor blood flow heart

Treatment:
Nitrate Drugs:
1) Nitroglycerin (glyceryl trinitrate) –> generates NO via
aldehyde dehydrogenase

Treatment causes Vasodilation, which improves blood flow

Question 13

Paracrine Control of Blood Flow: Autocoids vasoconstrictors

Answer 13

-Intrinsic control of blood flow

1) Prostaglandin: Thromboxane A2
- Vasoconstrictor
- Platelets form arachidonic acid via COX
- Clots

2) Serotonin 5HT:
- Vasoconstrictor
- Forms platelets during clotting

3) Prostaglandins
- Vasodilator/vasoconstrictors

Question 14

What are the possible negative effects of Autocoids

vasoconstrictors

Answer 14

-Coronary circulation: Atheromatous coronary arteries inappropriate platelet activation → 5-HT release can cause coronary vasospasm.

-Cerebral circulation: partly responsible cerebral vasospasm
(migraine, following a subarachnoid hemorrhage)

-Thrombosis: Clot within in blood vessel.
(Aspirin → prevent thrombosis in coronary atheroma)

-Thromboxane → platelet aggregation.
(Aspirin (in low doses) inhibits thromboxane formation in platelets.)

Question 15

Describe the role of histamine and bradykinin

Answer 15

• Both vasodilators
• Intrinsic control of blood flow

Histamine:

• Mast cell derived
• Inflammatory response
• Dilates arterioles
• Constricts veins

Bradykinin:
-Stimulates nociceptors
-Potent pain producer
(Via nitric oxide (NO)