Chapter 7: Vascular Control Flashcards
How are muscle filaments arranged in smooth muscles?
arranged more randomly, also actin and myosin filaments but not in organized sarcomere
List the structures that anchor actin filaments in smooth muscles
attach to inner cell surface with dense bands
attach to dense bodies attached to cell surface with intermediate filaments
List the intracellular steps leading to muscle contraction after Ca++ enters smooth muscle cells
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
What enzyme modulates the Ca++ sensitivity of smooth muscle cell activation? (i.e., changes contractility independent of actual Ca++ cc)
myosin phosphatase
What is the resting membrane potential in smooth muscle cells and what determines this?
- 40-65
rectifying K channel but also ATP-dependent K-channel
What is the name of the Ca++ channels activated by action potentials?
voltage-operated Ca channel
What channels cause repolarization in smooth muscle action potentials?
delayed K+ channels
Ca++-activated K+ channels
Explain the difference between electomechanical and pharmacomechanical coupling in smooth muscle cells. Explain their steps in detail
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
Explain how beta-2 adrenergic stimulation causes smooth muscle vasodilation
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
Explain how nitric oxide causes smooth muscle vasodilation
NO –> can diffuse into smooth muscle cells –> activates guanylyl cyclase –> activates cyclase –> GTP –> cGMP –> protein kinase G –> smooth muscle relaxation
What are the different categories of local influences of arterioles’ smooth muscle tone (4)
- metabolic
- stretch (transmural pressure
- other local chemicals
- endothelialc cell influence
What is the most important determinant of local metabolic regulation of arteriole tone?
O2 tissue concentration
low O2 –> vasodilation –> increased perfusion, and vice versa
List 5 factors influencing local metabolic tone of arteriole tone. How do they change in muscle tissue during exercise?
- O2
- pH/H+ cc
- CO2
- osmolarity
- K+
What is a potent vasodilator agent released by tissues under O2 deprivation or high metabolic activity
adenosine
Explain how nitric oxide is produced
in endothelial cells:
Ca+ cc increase –> triggers: L-arginne –> nitric oxide synthase –> NO
Name 3 things triggering NO production
Ca++ cc
acetylcholine (also bradykinin, VIP, sustance P)
flow related shear stress
Name 2 endothelial cell derived vasodilators other than NO
- endothelial-derived hyperpolarizing factor
- prostacyclin
What substance has the greatest known vasoconstrictor protency and where is it produced?
- endothelin
By what mechanism does histamine cause vasodilation?
same mechanism as beta-2 receptors (cAMP pathway)
What enzyme forms bradykinin and how does bradykinin affect smooth muscle tone?
kallikrein
stimulates NO release
How does the transmural pressure affect arteriolar smooth muscle tone?
stretch-receptors –> cause constriction i.e., myogenic response
Describe active and reactive hyperemia
active hyperemia - increase blood flow from tissue activity
reactive hyperemia –> transiently increased blood flow after removal of a restriction e.g., turniquet
What are the 3 theories for how autoregulation adapts to changes of MAP (~60-180 mm Hg)
(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
What is the tonic firing or neurogenic tone in arteriolar smooth muscles
sympathetic nerve endings constantly innervating arterioles to slightly restrict
Summarize what dominates the control of vascular tone of arterioles versus venous vessels
arterioles:
* basal tone
* metabolic
* sympathetic tone
venous:
* sympathetic tone
* internal pressure
* external compressing forces (skeletal muscle pump)
How does the parasympathetic nervous system affect arteriolar smooth muscle tone?
no direct nerve endings –> only circulating
How do moderate versus higher levels of norepinephrine affect arteriolar smooth muscle tone?
moderate levels trigger beta-2 receptors
high levels trigger alpha-1 receptors
Describe how RV and LV myocardial perfusion change during systole and diastole and why
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
Why do coronary arteries not constrict as a response to an increased sympathetic tone?
because increased sympathetic tone also increase the work of the heart –> increased metabolic vasodilators produced –> predominate in effect and cause vasodilation
What is the O2 extraction fraction of muscles tissue?
25-30%
What is the pulmonary capillary hydrostatic pressure?
8 mm Hg
