2.9. Local control of circulation. Characteristics of vascular smooth muscle. Myogenic, humoral, hormonal and neural control mechanisms.

Question 1

What is MYOGENIC TONE?

Answer 1

state of a muscle tone that originate from the muscle itself, rather than from the ANS

Question 2

I. Mechanism of local control
1. What are the 6 types of regulation for local control of circulation?

Answer 2

1- Autoregulation: (Bayliss effect)
2- Metabolic regulation
3-Endothelium-mediated relaxation
4-Humoral factors
5-Hormonal regulation of circulation
6-Neural regulation

Question 3

I. Mechanism of local control - Autoregulation
2A. Characteristics of Autoregulation

Answer 3

• Intrinsic ability of a body part to maintain a constant blood flow despite changes in arterial pressure
• It is an active process that requires an active reaction response from SMCs (occurs in the absence of neural and hormonal influences)
• Many organs show their own autoregulation curves (kidney, brain, skeletal muscle)
• The mechanism of autoregulation is achieved by dilating or constricting the SM of the small arteries + arterioles which have a myogenic tone

Question 4

I. Mechanism of local control - Autoregulation
2B. Mechanism of Autoregulation

Answer 4

Mechanism: Results from the increased tension (stretch) in the vessel wall, which contains SM, and then contract
1. Smooth muscle contains ‘’stretch-activated non-specific cation channels’’
2. When these channels are activateddepolarization
3. Depolarization activates VDCC L-type
-> influx of Ca2+
-> muscle contraction
(myogenic response)
-> vasoconstriction
4. Vasoconstriction will decrease the diameter / radius
-> resistance equation (resistance↑ = pressure↑)

Question 5

I. Mechanism of local control - Metabolic regulation
3A1. What are vasodilatory substances in metabolic regulation? What are their effects?

Answer 5

pO2↓, pCO2↑, lactate↑ (pH↓), adenosine↑, [K+]↑
-> Buildup of these metabolites -> vasodilation -> ↑ flow

Question 6

I. Mechanism of local control - Metabolic regulation
3A2. Why is adenosine a vasodilatory substance?

Answer 6

1. Adenosine (from ATP when metabolism↑).
   - In SMC: A2A, cAMP↑ = relaxation of SMCs (vasodilation)

Question 7

I. Mechanism of local control - Metabolic regulation
3A3. Why is K+ a vasodilatory substance?

Answer 7

K+: vasodilates arterioles by causing hyperpolarization of VSCMs

Question 8

I. Mechanism of local control - Metabolic regulation
3B. What is Functional hyperemia? What is the mechanism?

Answer 8

Functional hyperemia: occurs because blood flow is proportional to its metabolic activity

• If cell function↑
  -> metabolism↑
  -> metabolites↑
  -> vasodilation
  -> ↑ blood flow to cell to supply nutrients/remove wastes

(hen metabolic activity increases due to exercising muscle, or increased mental activity of brain, then the blood flow increases to that area to meet the increased metabolic demand (active hyperemia in skeletal m; up to 20-fold increase in local muscle blood flow!))

Question 9

I. Mechanism of local control - Metabolic regulation
3C. What is Reactive hyperemia (hypoxia)? What is the mechanism?

Answer 9

• An increase in blood flow in response to a prior period of arterial occlusion.
• When unblocked, blood flow increases by 4-7 times until the metabolite debt to be restored.
• The longer the period of occlusion, the greater the subsequent increase in blood flow.
  => When flow is blocked, metabolites build up and cause vasodilation. The longer the occlusion, the more metabolites produced

Question 10

I. Mechanism of local control - Endothelium-mediated relaxation
4A. What is the mechanism of Endothelium-mediated relaxation

Answer 10

Metabolism ↑
-> local metabolite concentration↑
-> resistance↓
-> local flow↓
-> shear stress causes activation of endothelial cells via receptor
-> endothelial cells produce NO
-> SM relaxation
-> vasodilation
-> ↑blood flow

Question 11

I. Mechanism of local control - Endothelium-mediated relaxation
4B. What is the role of NO in Endothelium-mediated relaxation

Answer 11

NO: synthesized by endothelial-derived
NO synthase
-> [cGMP]↑ + PKG
-> SMC relaxation
-> vasodilation

Question 12

I. Mechanism of local control - Endothelium-mediated relaxation
4C. What is the role of Opening of mechanosensitive Ca2+-channels in Endothelium-mediated relaxation?

Answer 12

Opening of mechanosensitive Ca2+-channels
-> PGI2
-> Gs-protein activation
-> [cAMP]↑
-> PKA
-> Phosphorylation of of MLCK
-> decreasing Ca2+ sensitivity
-> relaxation of SMCs
-> vasodilation

Question 13

I. Mechanism of local control - Endothelium-mediated relaxation
4D. How can K+-hyperpolarization of endothelial cell participate in Endothelium-mediated relaxation?

Answer 13

K+-hyperpolarization of endothelial cell can spread
-> Hyperpolarization of SMC
-> relaxation of SMC
-> vasodilation

Question 14

I. Mechanism of local control - Humoral factors
5. What are the humoral factors participate in local control of circulation? How do they work?

Answer 14

1. Vasodilator:
   - Histamine, serotonin, bradykinin
   -> endothelial cell activation
   -> NO production
   -> relaxation (vasodilation)
2. Vasoconstrictors:
   - ANGII, endothelin, thrombin, TXA2

Question 15

I. Mechanism of local control - Hormonal regulation of circulation
6A. What are the characteristics of Hormonal regulation of circulation?

Answer 15

Vasoconstrictors and vasodilators have Direct effects on smooth muscle, endothelial cells not involved

Question 16

I. Mechanism of local control - Hormonal regulation of circulation
6B. What are the vasoconstrictors that involve in Hormonal regulation of circulation?

Answer 16

1. Norepinephrine: α1-AR
   -> (Gq) -> Ca2+↑ -> SMC-vasoconstriction
2. Angiotensin II: activates AT1 receptors (Gq)
   -> SMC – vasoconstriction
3. Vasopressin (ADH) (Gq): in kidney
   -> water reabsorption↑BP
4. Histamine, serotonin: direct effects lead to Gq
5. (ACh): acts like a hormone, has its own receptor on SMCGq (M1,3,5) [Ca2+]
6. Endothelin

Question 17

I. Mechanism of local control - Hormonal regulation of circulation
6C. What are the 2 types of Vasodilators that involve in Hormonal regulation of circulation?

Answer 17

1. Endothelium-dependent
2. Endothelium-independent: (depends on receptor)

Question 18

I. Mechanism of local control - Hormonal regulation of circulation
6B1. The role of Norepinephrine in Hormonal regulation of circulation?

Answer 18

1. Norepinephrine: α1-AR
   -> (Gq) -> Ca2+↑ -> SMC-vasoconstriction

Question 19

I. Mechanism of local control - Hormonal regulation of circulation
6B2. The role of Angiotensin II in Hormonal regulation of circulation?

Answer 19

Angiotensin II: activates AT1 receptors (Gq)
-> SMC – vasoconstriction

Question 20

I. Mechanism of local control - Hormonal regulation of circulation
6B3. The role of Vasopressin (ADH) in Hormonal regulation of circulation?

Answer 20

Vasopressin (ADH) (Gq): in kidney
-> water reabsorption
-> ↑BP

Question 21

I. Mechanism of local control - Hormonal regulation of circulation
6B4. The role of Histamine, serotonin in Hormonal regulation of circulation?

Answer 21

Histamine, serotonin: direct effects lead to Gq

Question 22

I. Mechanism of local control - Hormonal regulation of circulation
6B5. The role of ACh in Hormonal regulation of circulation?

Answer 22

(ACh): acts like a hormone, has its own receptor on SMC
-> Gq (M1,3,5) [Ca2+]

Question 23

I. Mechanism of local control - Hormonal regulation of circulation
6C1. What are the Endothelium-dependent vasodilators that involve in Hormonal regulation of circulation?

Answer 23

1. Bradykinin + Vasoactive intestinal polypeptide (VIP)
2. Histamine (H1)
3. ACh (Ca2+-Gq-R = M1, M3, M5)
4. Substance P + Serotonin
5. Estrogen + insulin + testosterone

Question 24

I. Mechanism of local control - Hormonal regulation of circulation
6C2. What are the Endothelium-independent vasodilators that involve in Hormonal regulation of circulation?

Answer 24

1. Epinephrine: β2-receptor (Gs)
   -> cAMP
   -> PKA
   -> dephosphorylation of
   myosin light chain kinase
   -> SM relaxation
2. ANP: atrial natriuretic peptide
   -> cGMP increase
   -> PKG
   -> smooth muscle relaxation
3. Prostaglandin I2

Question 25

I. Mechanism of local control - Neural regulation
7. What is the mechanism of neural regulation in local control of circulation?

Answer 25

The most important neural regulation is the SYM innervation of vascular smooth muscle. Important in skin and skeletal muscle, but not important in the regulation of coronary, cerebral, pulmonary or renal circulations
=> Continuous vasoconstriction from the SYM nervous system contributes to the resting tone of smooth muscle