Chapter 7: Vascular Control

Question 1

How are muscle filaments arranged in smooth muscles?

Answer 1

arranged more randomly, also actin and myosin filaments but not in organized sarcomere

Question 2

List the structures that anchor actin filaments in smooth muscles

Answer 2

attach to inner cell surface with dense bands

attach to dense bodies attached to cell surface with intermediate filaments

Question 3

List the intracellular steps leading to muscle contraction after Ca++ enters smooth muscle cells

Answer 3

action potential or other trigger for IC Ca++ cc increase –> Ca++ calmodulin bind and build complex
–> complex activates myosin light chain kinase –> allows ATP to phosphorylate myosin light chains = cross-bridge site of myosin –> cross bridges to actin

Question 4

What enzyme modulates the Ca++ sensitivity of smooth muscle cell activation? (i.e., changes contractility independent of actual Ca++ cc)

Answer 4

myosin phosphatase

Question 5

What is the resting membrane potential in smooth muscle cells and what determines this?

Answer 5

• 40-65

rectifying K channel but also ATP-dependent K-channel

Question 6

What is the name of the Ca++ channels activated by action potentials?

Answer 6

voltage-operated Ca channel

Question 7

What channels cause repolarization in smooth muscle action potentials?

Answer 7

delayed K+ channels
Ca++-activated K+ channels

Question 8

Explain the difference between electomechanical and pharmacomechanical coupling in smooth muscle cells. Explain their steps in detail

Answer 8

electromechanical: action potential triggers opening of Ca++ channels on cell surface –> Ca++ moves into the cell and causes steps of actin/myosin binding (calmodulin)

pharmacomechanical coupling: hormone etc binds to surface receptor, usually G-protein coupled - can act in 2 ways:
* G-protein can open cell surface Ca++ channels
* G-protein can activate phospholipase C –> converts PIP2 to IP3 (second messanger) –> opens Ca++ channels of SR

Question 9

Explain how beta-2 adrenergic stimulation causes smooth muscle vasodilation

Answer 9

beta-2 receptor linked via G-protein to adenylate cyclase –>
ATP becomes cAMP –> activates protein kinase A –> phosphorylates surface efflux Ca++ channels –> Ca++ exits cell –> hyperpolarized + decrease contractile machinery sensitivity to Ca++

histamine and vasoactive intestinal peptide act through this same mechanism

Question 10

Explain how nitric oxide causes smooth muscle vasodilation

Answer 10

NO –> can diffuse into smooth muscle cells –> activates guanylyl cyclase –> activates cyclase –> GTP –> cGMP –> protein kinase G –> smooth muscle relaxation

Question 11

What are the different categories of local influences of arterioles’ smooth muscle tone (4)

Answer 11

• metabolic
• stretch (transmural pressure
• other local chemicals
• endothelialc cell influence

Question 12

What is the most important determinant of local metabolic regulation of arteriole tone?

Answer 12

O2 tissue concentration

low O2 –> vasodilation –> increased perfusion, and vice versa

Question 13

List 5 factors influencing local metabolic tone of arteriole tone. How do they change in muscle tissue during exercise?

Answer 13

• O2
• pH/H+ cc
• CO2
• osmolarity
• K+

Question 14

What is a potent vasodilator agent released by tissues under O2 deprivation or high metabolic activity

Answer 14

adenosine

Question 15

Explain how nitric oxide is produced

Answer 15

in endothelial cells:
Ca+ cc increase –> triggers: L-arginne –> nitric oxide synthase –> NO

Question 16

Name 3 things triggering NO production

Answer 16

Ca++ cc
acetylcholine (also bradykinin, VIP, sustance P)
flow related shear stress

Question 17

Name 2 endothelial cell derived vasodilators other than NO

Answer 17

• endothelial-derived hyperpolarizing factor
• prostacyclin

Question 18

What substance has the greatest known vasoconstrictor protency and where is it produced?

Answer 18

• endothelin

Question 19

By what mechanism does histamine cause vasodilation?

Answer 19

same mechanism as beta-2 receptors (cAMP pathway)

Question 20

What enzyme forms bradykinin and how does bradykinin affect smooth muscle tone?

Answer 20

kallikrein
stimulates NO release

Question 21

How does the transmural pressure affect arteriolar smooth muscle tone?

Answer 21

stretch-receptors –> cause constriction i.e., myogenic response

Question 22

Describe active and reactive hyperemia

Answer 22

active hyperemia - increase blood flow from tissue activity
reactive hyperemia –> transiently increased blood flow after removal of a restriction e.g., turniquet

Question 23

What are the 3 theories for how autoregulation adapts to changes of MAP (~60-180 mm Hg)

Answer 23

(1) initially increased blood flow –> washed out metabolic vasodilators
(2) stetch-receptor resposne, increased blood flow will initialy stretch the arterioles
(3) tissue pressure increase –> initially incresed blood flow causes increased capillary efflux –> interstitial tissue pressure increases –> compresses vessels

Question 24

What is the tonic firing or neurogenic tone in arteriolar smooth muscles

Answer 24

sympathetic nerve endings constantly innervating arterioles to slightly restrict

Question 25

Summarize what dominates the control of vascular tone of arterioles versus venous vessels

Answer 25

arterioles:
* basal tone
* metabolic
* sympathetic tone

venous:
* sympathetic tone
* internal pressure
* external compressing forces (skeletal muscle pump)

Question 25

How does the parasympathetic nervous system affect arteriolar smooth muscle tone?

Answer 25

no direct nerve endings –> only circulating

Question 25

How do moderate versus higher levels of norepinephrine affect arteriolar smooth muscle tone?

Answer 25

moderate levels trigger beta-2 receptors
high levels trigger alpha-1 receptors

Question 26

Describe how RV and LV myocardial perfusion change during systole and diastole and why

Answer 26

LV: perfused only during diastole, systolic pressure is high in LV and compresses the coronary vessels - impedes forward flow

RV: systolic pressure is lower and coronary vessels are less compressed

Question 27

Why do coronary arteries not constrict as a response to an increased sympathetic tone?

Answer 27

because increased sympathetic tone also increase the work of the heart –> increased metabolic vasodilators produced –> predominate in effect and cause vasodilation

Question 28

What is the O2 extraction fraction of muscles tissue?

Answer 28

25-30%

Question 29

What is the pulmonary capillary hydrostatic pressure?

Answer 29

8 mm Hg