Vascular control Flashcards
What tissues make up blood vessels?
Endothelium
Elastic tissues
Smooth muscle
Fibrous (collagenous) tissues
What is the layer that all blood vessels have?
Endothelium
How is vascular smooth muscle layered?
Circular layers which are capable of vasoconstric/dialtion
What is unique of VSM?
Must sustain active tention for prolonged periods or time
What is vascular tone?
General contractile state of vessel or vascular region
- used as individual VSM cells activation
What are the short term adjustments of VSM?
Regulating contractile activity of VSM cells
What is a long term adjustment to VSM?
Adaptations to both active and passive components (Structural CT) of vascular wall
What are the differences of VSM and cardiac/skeletal muscle?
- Contract/relax more slowly
- Contractile activity as result of either AP or resting membrane potential
- Can change contractile activity in absence of any changes in membrane potential
- Can maintain tension for prolonged periods at low energy cost
- Can be activated by stretch
What is the contractile process of VSM like?
- Ca2+ complexes with calmodulin
- This complex activates myosin light-chain kinase
- MLC kinase allows ATP to phosphorylate MLC protein
- MLC phosphorylation enables cross-bridge formation & cycling, during which energy from ATP is utilized for tension development/shortening
What are some characteristics of VSM membrane potentials?
- 40-(-65) like most cells
- due to K+ perm (inward rectifiers)
- AP are predominately a result of slow inward Ca2+ (slow type)
What is another unique thing about VSM activation?
Stretch-sensitive cation channels involved in cellular response of muscle stretch.
What is VSM electromechanical coupling?
SM membrane contains voltage operated Ca channels (VOC’s)
- partially activated at low resting MP of VSM. Thus changing resting potential can alter basal contractile state
What leads to contraction of VSM?
Membrane depolarize leads to VOCs–> Ca2+ in and contraction
What cause VSM relaxation?
Hyperpolarization
What is VSM pharmacomechanical coupling?
SM contraction without change in membrane potential
- Receptor operated Ca2= channels (ROC)
- Formation of inositol triphosphate opens CA2+ channels on SR
Need Receptor for GTP binding proteins
What do chemical vasodilators target?
G protein couple receptors
-B2 receptors
What does binding to B2 receptors cause? What binds to them?
Leads to increase cAMP/cGMP activates protein Kinase A to cause phosphorylation of many proteins
- stimulate Ca EFFLUX
- membrane hyperpole
- decrease contractile machinery sensitivity to Ca
abnormal high levels of epi
Histamine
Vasoactive intestinal peptide
What strongly influences control of arterial tone?
local metabolic needs in region their reside
What is basal tone?
Arteriole remains in a state of partial constriction after removal of external influences
- intrinsic tone
What are some external influences on basal tone?
Local
Neural
Hormonal
What does continual internal pressure on arterioles lead too?
Result of tonic production of local vasoconstrictors by endothelial cells that line the inner surface
What are the local influences that control arterial tone?
Metabolic
Endothelial cells
Other chemicals
Transmural pressure
What is the most important means of local flow control?
VSM being subject to chemical composition of organ/tissue they serve
What are some things that simulate vasodilation?
low: o2
high: CO2, H+, K+
* ** all because of exercise for example
Release of adenosine
What doe endothelial cells produce to influence arterial tone?
Nitric oxide
-Easily diffuses across cell membrane and stimulates cGMP production–> cGMP inhibits Ca2+ entry, activates K+ channels leading to hyperpolarization, activates MLC phosphatase
What other factors increase NO production?
acetylcholine, bradykinin, vasoactive intestinal peptide, supstance P
less known Prostacyclin
Endothelial derive hyperpolarizing factor
What are some local chemicals that affect arterial tone?
- Prostaglandins and thromboxanes
- leukotrienes
- Histamine
- Bradykinin
Can prostaglandins and thrombaxanes be both vasodialtors and constrictors?
yes
What is the importance of prostaglandins involved with platelets?
Important vasoconstrictors and platelet aggregating response to vascular injury and hemostatic (flow stopping and antibleeding)
What is transmural pressure?
Arterioles are actively and passively response to changes in transmural pressure
What is an example of transmural pressure?
Slight dilation leads to VSM constriction and reverses dilation
- or vice versa
How does this response to pressure occur?
Activation of stretch sensitive ion channels on arteriolar VSM cells
What is hyperemia?
Flow rate
What is active hyperemia?
In organs with highly variable metabolic rate, the blood flow closely follows the tissue’s metabolic rate!`
What is reactive hyperemia?
Higher than normal blood flow after removal of restriction (tourniquet)
-Duration dependent on severity of occlusion and metabolic needs
What is the most important means of reflex control of vasculature?
Neural influences-Vasoconstrictor nerves
- increase activity leads to increased vasoconstriction
What is neurogenic tone?
Continual firing (tonic firing) activity increases the normal contractile tone of arterioles to above basal
What does NE do to arterial tone?
-Increase tone after combining with α1-adrenergic receptor on smooth muscle cells
What do alpha1-adrenergic receptors bind and what does this cause?
Catacholamines
Lots of these receptors in vasculature, less sensitive to Epi
VASOCONSTRICTION
What doe Beta2 adrenergic receptors bind and what is its bind?
Catecholamines but not NE
- Only in arterioles of SOME organs
- Fewer of these in vasculature, more sensitive to Epi than α1
VASODILATION
What does vasopressin and angiotensin II do to arterioles?
Vasoconstrictor
How does one control the venous tone?
Volume
- not subject to local metabolic needs
Differences between VSM in veins compared to arterioles?
- Very little basal tone normally in dilated state (in the absence of any external influences! This is almost never the case in the in tact system though!!!)
- Vasodilator metabolites may accumulate in the tissues and have little effect on veins because of this
- Thin walls = more susceptible to physical influences
- External compressional force is important determinant of venous volume
- Ex: skeletal muscle pump helps return blood to heart during exercise
What is the job of arterioles?
to efficiently distribute the CO amount tissues with diff current needs
What is the job of veins?
To regulate the distribution of blood volume and cardiac filling
What are 2 ways to contract VSM?
- Increase intracellular Ca2+
- Ca2+ sensitivity of the contractile machinery
(increasing MLC Phosphatase)
What often leads to VSM relaxation and why?
increasing intracellular conc. of cyclic nucleotides.
- NET state of phosphorylation of MLC depends on ratio between Calcium dependent and independent MLC phosphatases.
What is a VOC?
Voltage operated channel
- electromechanical coupling
- depolarization leads to contraction
What do vasoconstrictors target on VSM?
alpha 1 (a1) adrenergic receptor
- binds NE
- ROCs open and influx of Ca2+ leading to greater contraction of the VSM
- Or via IP3 to stimulate specific channels on SR to release Ca2+
When interstitial fluid is low in O2 what does that mean?
Using O2 faster than it is being supplied by the blood.
What does high O2 do to vessels?
Vasoconstrictor
Cells that are deprived of O2 release what?
Adenosine
- vasodialate
What represents the most important means of local blood flow?
local metabolic mechanisms
- increase interstitial vasodilators leads to vasodilation and diffusion of dilators into the blood
What does acetylecholine do to endothelial cells and non endothelial cells?
Intact vessels- vasodilator
Vasoconstrict of vessels stripped of endothelial lining
What produces NO?
Endothelial cells
Nitric oxide synthetase which is activated by high intracellular levels of Ca2+ (means it has been contracting)
Which pathway does histamine use to vasodilate?
cAMP pathway
- makes vasculature porous and leads to edema. Stimulate sensory nerves to cause pain and itching
What causes blood flow autoregulation?
local metabolic feedback and myogenic mechanisms
What serves as the backbone to system for controlling total peripheral resistance?
Sympathetic vasoconstriction innervation
Do vessels have parasympathetic innervation?
no
Where are Beta 1 adrenergic receptors found and what is their purpose?
found in the heart to increase HR and contractibility
What are the major controllers arterial tone?
Basal tone
Local metobolic vasodilator factors
Sympathetic vasoconstrictor nerves by Alpha 1
What are the major controllers of veinous tone/
Internal pressure
Sympathetic vasoconstrictor nerves
External compression from muscles
