Week 08 Lect 1 - Circulatory Regulation: Local Reg & Hormones (Dustin) Flashcards
What is the O2 content in the arterial supply?
Venous supply?
So what is the average arteriovenous O2 difference (AVDO2)?
Arterial: 200 mL/L
Venous: 150 mL/L
AVDO2 = 200 - 150 = 50mL/L
What are the 3 mechanisms of circulatory system control?
- Local Control (main topic of lecture)
- Hormonal/Humoral Regulation (slow process)
- Reflex Regulation (CNS involved)
What is the Bayliss Effect?
What is the (general) sequence of events in this effect?
Autoregulation involving myogenic tone,
characteristic of small arteries & arterioles
With a decrease in pressure, you would normally expect flow to decrease.
However, here the vessel musculature relaxes, vessel radius increases, so resistance goes down, which means flow is maintained/autoregulated
(the opposite happens with increase in pressure)
What specific changes occur in Bayliss effect during an increase in pressure?
Pressure increases -> tension on wall increases
- > mechanosensitive cation channels open
- > depolarization
- > L-type Calcium channels open
- > [Ca2+] increases
–> Vasoconstriction
Also, Transient Receptor Potential (TRP) Channels open
–> additional increase in [Ca2+]
What does the graph for the effect of metabolism on blood flow look like?
Beyond the normal level, metabolism increases with blood flow roughly linearly
What kind of control do the precapillary sphincter and smooth muscle of laminal arterioles/metarterioles get?
They don’t have any sympathetic innervation,
so they get local control
What is the general sequence of events when cell function is increased in regards to circulatory regulation?
(referring to when a cell starts working harder to perform a task)
Cell function increases -> metabolism increases
-> metabolite concentrations increase
–> vasodilation
What are the common local changes in metabolite concentrations that occurs during increased cell function?
Increased cell function leads to…
- pO2 decrease
- pCO2 increase
- lactic acid concentration increase / pH decrease
- adenosine increase
- [Potassium] increase
What is the name for when increased metabolite concentrations during high cellular activity leads to blood vessel dilation and increased flow?
Functional Hyperemia
(may be called Metabolic or Active Hyperemia too)
What is reactive hyperemia?
Why does it occur?
When a vessel is cut off from circulation (as in clamping or some other blockage), but after some time flow is restored, flow will initially be increased proportionally to how long/severly the vessel was occluded
Occurs because of the local control of metabolites that built up during the time of occlusion, causing vasodilation. But when blood flow is restored and metabolites are returned to normal concentrations, the vasodilatory effect ends and flow goes back to normal
What are the endothelium-mediated regulators of vasodilation?
(considering local effects here)
Prostaglandin I2
Nitrous Oxide (NO)
What are the factors that lead to nitrous oxide production
What is the ultimate effect?
Metabolism increases -> local [metabolite] increases
- > Resistance of vessel decreases
- > local flow increases
- > Shear Stress
- > endothelial cells activate
- > Nitrous Oxide production increases
–> vasodilation
What occurs specifically with an increase in nitrous oxide?
[NO] increase -> [cGMP] increase
- > Protein Kinase G
- > Relaxation of smooth muscle
What are the chain of events that result from prostaglandin I2?
Prostaglandin I2 -> Gs activation
- > [cAMP] increase
- > Protein Kinase A
- > Relaxation of Smooth Muscle
What is retrograde vasodilation?
Propagation of vasodilation to upstream arterioles that are critical for regional flow
What are some chemical signals to increase nitrous oxide production?
Histamine
Serotonin
(plus some other hormones)
All lead to endothelial cell activation, which -> NO production -> vasodilation
What are the endothelium-mediated vasoconstrictors?
considering local effects here
Endothelin
Angiotensin II
What are we referring to in order to differentiate hormonal regulation of circulation from local regulation?
Hormonal regulation is reffering to direct effects on smooth muscle; endothelial cells are not involved
What are 6 hormonal regulation vasoconstrictors?
- Norepinephrine (NE)
- Angiotensin II
- Vasopressin (aka antidiuretic hormone)
- Serotonin, Histamine (opposite effect on hormonal level!!)
- Endothelin
- Epinephrine (only at high concentrations! otherwise = vasodilator)
(remember NAVSHEE)
What are the effects of norepinephrine?
Where does it come from?
NE affects the alpha-1 adrenergic receptor
- > Gq activation
- > cytoplasmic [Ca2+] increase
–> vasoconstriction
Comes from sympathetic system or adrenal gland
What sequence of precursors leads to the development of angiotensin II?
angiotensinogen (+ enzyme renin) -> angiotensin I
-> angiotensin II
What receptor does angiotensin II activate, and what are the effects?
activates AT1 receptor (a Gq coupled receptor in smooth muscle)
-> vasoconstriction
What receptor does vasopressin bind to in order to affect blood pressure?
Under what conditions is vasopressin’s action important?
V1 receptor -> Gq activation -> vasoconstriction
normally not relevant, but occurs when BP is very low
(V2 receptor is for antidiuretic hormone effect)
What are 3 hormonal regulation vasodilators?
- Epinephrine (in low concentrations only! high conc -> vasoconstriction)
- ANP: Atrial Natriuretic Peptide
- Prostaglandin I2
What differing receptors explains why epinephrine can have both vasodilation and vasoconstriction effects?
Beta2 adrenergic receptors -> Gs activation -> cAMP increase -> vasodilation
- epinephrine has higher beta2 binding affinity than NE, and low concentrations of epinephrine bond well to Beta 2 receptors
However, there are many more alpha-1 than beta2 adrenergic receptors in the body
alpha1 -> Gq -> vasoconstriction
- so, high [epinephrine] -> alpha 1 effect overpowers beta2
- -> vasoconstriction
Where is ANP produced in the body?
What are its effects?
ANP: Atrial Natriuretic Peptide
Produced in low pressure part of circulatory system (heart atria) in response to increased venous pressure
ANP -> [cGMP] increase -> vasodilation
