CV Flashcards
1% increase in endo function can cause _% increase in life expectancy?
13%
list ways endothelial function can be measured
IVUS, laser doppler flowmetry, blood biomarkers (ICAM, VCAM, NO)
endothelium-derived chemicals (vasodilatory)
NO, PGs, endothelium-derived hyperpolarising factors
endothelium-derived chemicals (vasoconstricting)
endothelin, prostanoids
3 types of NOS
neuronal, inducible, endothelial
how does eNOS produce NO?
conversion of L-arginine and O2 into L-citrulline and NO
what maintains eNOS in its dimeric form?
BH4
why is BH4 necessary for eNOS function?
Keeps eNOS in dimeric form, if monomeric, O2 gets converted into O2- (ROS) and NO cannot be produced
how does NO bring about vasodilation?
NO in EC -> VSMC, activates sGC which catalyses cGMP -> activates PKG, which brings about vasodilatory responses
what does PKG do?
inhibits Ca release from SR, activates ca-dependent K+ channel which then inhibits LTCCs, and decreases sensitivity of myosin (reducing its phos and thus causing relaxation)
what management potential was highlighted in the paper
anti-hypertensive targeting. specifically for patients who are insensitive to dietary salt or who do not react effectively to ACEi/ARBs
what do the findings suggest about NSAIDS’ hypertensive SE?
likely brought about as a result of decreased PG production by COX inhibition, and thus reduced activation of EP4 (etc), therefore less NO produced and vasorelaxation is reduced.
key paper conclusions
EP4 activation enhances vasodilation in a NO/eNOS-dependent manner via the AMPK mechanism