Manipulation of Vascular tone Flashcards
What are the 3 main cell surface receptors
- Ion channels
- G-proteins
- Enzyme linked
Describe ion channels
ligand binds receptor, channel opens and ions move through
Describe G-protein coupled receptors
Signalling molecule binds and brings proteins together, activates effector and causes change inside the cell
Describe the enzyme-linked receptors
Signalling molecule binds and sets off a series of intracellular messengers
How does hydrophobic signalling molecules act on the nucleus
Cross the lipid bilayer, where they attach to a receptor to forma receptor hormone complex. Receptor hormone complex then affects protein synthesis to make more of the hormone
How do hydrophilic signalling work
Needs help to cross the lipid bilayer
Attaches a membrane receptor, which then signals an intracellular second messenger
What are the main elements that make up vascular smooth muscle ultrastructure
- Endothelial cell
- Internal elastic lamina
- Vascular smooth muscle cell
What do vascular smooth muscle cells form
A functional syncytium
Which vessel of the circulatory system have lots of VSM cells
Arterioles
What effect is a result of the elastic nature of arterioles
The windkessel effect, ensures constant flow
What is key in influencing vascular smooth muscle tone
Intracellular calcium
What endothelial derived factors influence vasomotor tone
- Prostanoids
- Peptides (angiotensin-II)
- Endothelial derived hyperpolarising factors
- Endothelin
- Nitric oxide
What type of cell surface receptors do prostoglandind use
G-protein coupled receptors, requiring an intracellular
What is angiotensin 11
potent vasoconstrictor
Where is angiotensin I converted to angiotensin II
The surface of an endothelial cell
What is the renin-angiotensin-aldosterone system
Body’s response to low BP. Renin, which is released primarily by the kidneys, stimulates the formation of angiotensin in blood and tissues, which in turn stimulates the release of aldosterone from the adrenal cortex. This causes the body to retain water and increase BP.
What is nitric oxide and what is it released by
A potent vasodilator
Released by sheer stress
How does nitric oxide work
- Diffuses into the vascular smooth muscle cell
- stimulates cGMP through soluble guanylate cyclase
- cGMP activates protein kinase G
- Protein kinase G stimulates the reuptake of cytosolic calcium and the open of calcium activated potassium channels
- Cytosolic Calcium levels fall
- MLCK activity decreases
- Decreased cross bridge
- Relax
What do endothelins do
Potent mediators of vasoconstriction
How is local blood flow determined
By the relative open/closed state of arterioles
What is Poiseuille’s law
Flow = [Pressure Difference x (pi radius^4)] / (8Length*Viscosity)
I.e. a decrease by 1mm creates a 16th fold increase in resistance
How do metabolities induce vasodilation
- Low O2 = build up of local metabolites
- low O2 will induce vasodilation
- Will go into reactive hyperaemia, to clear built up metabolites
What occurs in chronic hypoxia
Induces vascular growth (angiogenisis)
