Flashcards in Drugs affecting the vasculature and blood pressure Deck (114)
what is the role of endothelial cells?
provide a diffusion barrier but also inhibits platelet activation
more importantly - it can control the relaxation and contraction of smooth muscle cells
how do smooth muscle cells contract? the mechanisms is essentially the same as airway smooth muscle. Step 1-
how does calcium enter the SMC?
L-type channels or GPCR q11
what does calcium bind to once in the SMcell?
what does the Ca/calmodulin do?
converts MLCK into active MLCK
what does active MLCK do?
phosphorylates MLC causing contraction
which molecules is responsible for relaxation in SMC?
what does cGMP do?
coverts MLC phosphatase into active form
what does active MLC phosphatase do?
dephosphorylaes MLC causing relaxation
which substances act on the endothelium to cause vasodilatation?
what do vasodilators on endotheliam dio?
allow GPCR to let in Ca into the cell ?
what does Ca in endothelial cells do?
binds to calmodulin
what does the Ca calmodulin complex do in endothlelial cells ?
activates nitric oxide synthase
what does nitric oxide synthase do?
converts L-arginine and oxygen to NO and citrulline
what does the NO producedby the endothelial cells then do?
diffuses into the SMC neighbouring it
what does NO in SMC do?
activates guanylate cyclase which converts GTP to cGMP
what does cGMP do?
causes relaxation through mechanism previously
what else can cGMP do?
activate protein kinase G activates Ca dependent K channels - causing K to leave and thus hyperpolarisation
what do organic nitrates do?
when metabolised they relesase NO into SMC and cause relaxation as above
in small doses what do organic nitrates do?
cause venorelaxation - decreases SV
what does small doses of organic nitrates do to the HR?
increase it so CO is maintained the same
what do organic nitrates do in larger doses?
cause arteriolar dilatation
what does arteriola dilatation cause?
decreases the arterial pressure so reduces afterload
- also decreases pulse wave reflection
why are organic nitrates useful in angina?
they cause decreased myocardial oxygen requirement via
1) decreased preload
2) decreased afterload
3) improved perfusion of the ischaemic zone
how do Organic nitrates cause improved perfusion to ischaemic zones?
they cause dilatation of collateral vessels
what are organic nitrates used in?
angina and acute coronary syndrome
what is the danger in unstable angina?
danger that a cap of atheromatous plaque is going to form a thrombus
what are the two examples of ONs?
GTN and Isosorbide mononitrate
what is GTn most effective in?
prevention rather than relief