Flashcards in Control of Vascular Resistance Deck (19)
What leads to release of NO? Mechanism?
ACh. Ca2+ influx activates eNos, argine -> citrilline producing NO. NO diffused out of endothelium into muscle cell where it activates guanylyl cyclase. GTP -> GMP and PKC leading to relaxation
Other endothelium derived vasodilators?
EDHF - hyperpolarises the membrane, preventing contraction
Prostacyclin - generated from AA by COX, reduces intracellular Ca2+ via cAMP pathway and MLCK activity
Endothelium derived vasoconstrictor?
Endothelin - binds ET-R on SMC to increase intracellular Ca2+ and SMC contraction
What is the effect of atherosclerosis?
Reduces production of NO. Vasculature will still react in the same way as non-pathologica tissue if exposed to an NO donor.
Uncoupling of NO synthesis due to lack of availability of BH4 or arginine produces superoxide which can further damage the endothelium.
Why control blood flow?
Reduce cardiac work
Adequately meet metabolic needs
How is blood flow controlled? (general)
Where do metabolic vasodilators act?
Terminal resistance arterioles
3 mechanisms of autoregulation?
Tissue fluid pressure
Proposed by Bayliss, 1902. Increased perfusion pressure increases wall tension, VSMC contracts when stretched and relaxes when passively shortened. Action purely myogenic, no mediators required. Involves activation of L-type Ca2+ channels and PKC to enhance contractility. Braking mechanism includes Ca2+ activated K+ channels and shear induced NO release.
Tissue pressure mechanism of autoregulation?
Increased perfusion pressure increases flow out of capillaries, increasing tissue vol and therefore pressure. This reduces the transmural pressure distending the vessel, increasing vessel resistance and therefore reducing flow.
Vasodilator washout mechanism of autoregulation?
Increased blood flow washes out local vasodilators
What is active/metabolic hyperaemia?
Increased tissue metabolic activity causes local vasodilation due to release of local metabolites. Eg adenosine, K+, H+, hypoxia, Pi, hyperosmolarity, CO2
Due to myogenic response and local accumulation of vasodilators.
Risk of re-perfusion injury.
Effect increased interstitial K+?
Effect of changes interstital ADP/ATP/adenosine?
Effect of decreased interstitial ATP?
Released adenosine, decreased intracellular ATP
Depolarisation, opens VGCC
Opens K-ATP channels
Effect of histamine?
Vasodilator. Released from mast cells and leukocytes in response to injury. Extravasation of plasma proteins. Leads to oedema and inflammation. Increases NO release fro endothelium via Histamine-R.
Effects of bradykinin?
Vasodilator formed by enzyme kallikrein during inflammation, contributes to hyperaemia by increasing No release from endothelium. Sensitises nerves.
Derivative of tryptophan, released from platelets to cause vasoconstriction of arteries and veins.
Formed from AA and released from platelets to cause vasoconstriction. Aspirin inhibits synthesis.