Lecture 14 - Elements of Vascular and Microvascular Function Flashcards
In what vessels is the highest resistance?
Arterioles
What are the 3 active functions of smooth muscle cells? Describe each.
- Contractile function to induce changes in capacitance and resistance of vessels
- Plasticity, meaning they can undergo hypertrophy, proliferate, and undergo phenotypic changes in vascular disease and during development
- Secretory function: during vascular disease they can form and release matrix, growth factors, and proteases
What determines vascular smooth muscle tone?
Free intracellular [Ca++]
Are smooth muscle cells electrically or chemically induced to contract?
BOTH
How does muscle contraction in smooth muscle compare to that in skeletal/cardiac muscle?
Process is much slower because of series of reactions (involving MLCK) and decreased myosin ATPase activity
Definition of microcirculation?
Circulation made of vessels in the 10-200 micron range in diameter
Describe the smooth muscle of metarterioles.
Discontinuous smooth muscle surrounding them
When can vessels of the microcirculation collapse?
Below a critical opening pressure
Other name for critical opening pressure?
Critical closing pressure
What is rarefaction?
Reduced density of patent vessels as a result of a collapse of vessels of the microcirculation
Describe the smooth muscle of arterioles.
Continuous smooth muscle surrounding them
What do we find between arterioles/metarterioles and capillaries? Purpose?
Precapillary sphincters = band of smooth muscle at the arteriolar end of capillaries
Purpose = band of smooth muscle that determines local resistance thus blood flow to the given capillary bed
How do precapillary sphincters respond to local conditions?
They are exposed to the same environment as the tissues the capillaries are supplying so can regulate blood flow based on secretions by these cells
For what 2 reasons are arteries not designed to regulate blood flow to tissues?
- They have a lot of smooth muscle, but not enough to truly regulate their size efficiently
- They are not in the local environment of the tissues being supplied so cannot respond to changes in the environment
What is the modern view of the endothelium?
Dynamic tissue that will have a varying structure depending on what tissue it’s in
What are the 4 types of compounds secreted by endothelial cells? Give examples for each type.
- Endothelial derived vasodilators: NO, prostacyclin (PGI2)
- Endothelial-derived vasoconstrictors: endothelin
- Anti-thrombogenic/aggregatory factors for platelets
- Anti-mitogenic factors for vascular smooth muscle to maintain their structure
Describe 2 metabolic functions of endothelial cells.
Processing of vasoactive factors:
- Production of angiotensin II from angiotensin I by angiotensin-converting enzyme (ACE)
- Breakdown of bradykinin by angiotensin-converting enzyme (ACE)
In what circumstances do endothelial undergo angiogenesis?
- In response to injury and ischemia
- Embryonic development
- Tumorigenesis
3 active functions of endothelial cells?
- Secretory function
- Metabolic function
- Plasticity
What are the 2 methods for causing either vasoconstriction or vasodilation of smooth muscles of vessels? Describe each briefly.
- Endothelium-dependent: ligand binding to endothelium receptors => production of endothelial relaxing or constricting factors which diffuse to smooth muscle
- Endothelium independent: direct binding to receptor on smooth muscle
What are 5 examples of an endothelium independent vasoconstrictors?
- Vasopressin (AVP)
- NE
- EPI
- Angiotensin II (but requires ACE in endothelium to go from angiotensin I to II)
- Endothelin
What are 4 example of an endothelium independent vasodilator?
- Atrial natriuretic peptide (ANP)
- NO
- PGI2
- EDHF
What are 6 examples of an endothelium dependent vasodilator? What do they cause the endothelium to release?
- Histamine
- ACh
- Bradykinin
- Purinergics (e.g. adenosine)
- Serotonin
- Shear stress
=> endothelium releases NO, PGI2, and EDHF
What is shear stress? What is directly related to?
A frictional force tangential to the direction of a flowing fluid, the force of which is directly related to the fluid’s viscosity and the pressure gradient
What are 2 examples of an endothelium dependent vasoconstriction? What do they cause the endothelium to release?
- Pulmonary HT
- Vessel injury
=> endothelium releases endothelin
What are the steps of the mechanism of endothelium-dependent vasodilation with NO?
- Ligands/shear stress on endothelial cell increase intracellular Ca++
- Activation of eNOS = NO synthase (Ca++ dependent)
- eNOS: O2 + L-arginine => NO + L-citrulline
- NO diffuses to smooth muscle cell and acts on soluble guanylate cyclase to activate it
- GC: cGTP => cGMP
- cGMP decreases free Ca++ in smooth muscle cell => RELAXATION
What is the half life of NO? What does this mean?
6 s => only affects nearby cells despite the fact is diffuses readily = potent LOCAL vasodilator
CAN NO REGULATE BP? Why?
NOPE
Because of very short half-life
What kind of molecule is NO?
Free radical gas
Is NO lipid or water soluble?
Lipid
What kind of enzyme is eNOS? What does this mean?
Constitutive enzyme => produced in constant amounts without regard to the physiological demand
What is iNOS?
Inducible NO synthase
Other than activating eNOS, what else can free intracellular Ca++ induce in endothelial cells? Describe the mechanism.
Increase conversion of arachodonic acid to prostacyclin (PGI2) by COX => activates AC in smooth muscle: ATP => cAMP => decrease of Ca++ in smooth muscle cells => RELAXATION
How long does PGI2 lasts?
1 circulation through the body, also a short-lived vasodilator
Which is the more important vasodilator: NO or PGI2?
NO
What are the 3 endothelium-dependent relaxation mechanisms?
- NO secretion by endothelium
- PGI2 secretion by endothelium
- EDHF secretion by endothelium
What does EDHF stand for?
Endothelium-dependent hyperpolarizing factor
Describe how EDHF works.
The endothelium releases EDHF which causes hyperpolarization of smooth muscle cells by causing K+ outflow => relaxation
What effect would the endothelium dependent vasodilators have without the presence of an endothelium? Purpose?
They would cause constriction by direct actions on vascular smooth muscle
Ligands having direct access to the smooth muscle means that something is wrong with the endothelium (like damage), and flow should not be increased to this part of the vessel - this is an inappropriate response when the damage is due to HT of arteriosclerosis because it just makes the situation worse
What could cause dysfunctional endothelium?
Arteriosclerosis or other vascular diseases
Do blood vessels receive parasympathetic innervation?
NOPE, except for GIT and sex organs
How do platelets react with the endothelium?
- Healthy endothelium: platelets cannot stick because they make NO and prostacyclins. If they do stick, they will release ADP and serotonin, which will further relax the smooth muscle cell
- Unhealthy/damaged endothelium: platelets are activated by tissue below endothelium and aggregate on smooth muscle cells and secrete serotonin and thromboxane A2 (which also causes further platelet aggregation via + feedback) to contract them
What are the 2 lymphatic ducts? % drainage in each?
- Thoracic duct (75%)
2. Right lymphatic duct (25%)
What forces cause exchange of molecules at capillaries?
Starling forces:
- Net filtration at arteriolar end
- Net reabsorption at venular end
Which of the Starling forces is responsible for lymph fluid flow?
Pressure gradient between interstitial hydrostatic pressure and lymphatic capillary hydrostatic pressure
Describe the resistance in the capillaries.
They have an intrinsic resistance that decreases throughout the capillaries
What determines the tone of a vessel?
Free intracellular Ca++
Other name for NO?
Endothelium dependent relaxing factor
