Endothelial Cell Function Flashcards
4 Functions of Endothelial Cells
Selective barriers w/ roles in inflammation including edema and diapedesis
Prevention of clotting and platelet adhesion (glycocalyx)
Reg of vascular smooth muscle contraction
Secretion of prots
P-selectin
One of prots covered by glycocalyx, when exposed platelets and RBCs can stick and aggregate
iNOS vs. c/eNOS
Stimulated by inflammation and not Ca dependent vs. Ca dependent and somewhat constitutive in normal vessels
Blood Flow Shear
Bends cilia, activating Ca channels to activate cNOS. Leads to endothelials orienting in direction of sheer
NO Effect on Smooth Muscles
Activate GC to make cGMP -> PKG -> MLC phosphatase -> IP3 Rs in SR -> activate K+ channels -> relaxation
PDE (2)
Breaks down cGMP so leads to smooth muscle contraction. Viagra inhibits
4 NO Production from R Activat
M3 ACh R (erection)
H1 Histamine R (injury)
Bradykinin R
Leukotrienes
NO Production
NOS Forms from conversion of Arg to Citrulline
Reactivity of NO (2)
Unpaired electron so free radical. reacts w/ superoxide to produce peroxynitrite ROS
Chelates w/ Fe to bind Hb and Mb very well
Sodium Nitroprusside
NO donor used in hypertensive crisis as vasodilator, has NO attached to Fe
Exercise
Activates eNOS and nNOS in endothelials and skeletal, respectively
3 Pathways from Arachidonic Acid
Can either go COX to produce PGI2 (relax) or TXA2 (contract), or leukotriene Endothelium-derived hyperpolarizing factor (EDHF, relax)
Inhibition of Platelet Aggregation (2 paths)
NO stimulates Ca decrease through its route, and prostacyclin goes via AC -> cAMP -> PKA to decrease Ca as well
Endothelin-1
Vasoconstrictor stored as propep in endothelial cells. When released, has biphasic action by first binding neg feedback ETb Rs on releasing endothelial cell which stimulates NOS. Then has direct effect on VSM cell by activating ETb/ETa/Gq to go PLC -> increased Ca -> constriction
Bosentan
ET-1 Antagonist to treat pulmonary hypertension
