Nitric oxide Flashcards
Family of NO synthases
eNOS
nNOS
iNOS
eNOS
Endothelial nitric oxide synthase
Accounts for endothelium dependant vasodilation
nNOS
Neuronal nitric oxide synthase
Accounts for smooth muscle relaxation in specialised blood vessels,gut and reproductive tissues.
Mediated by nitrergic nerves.
iNOS
Inducable nitric oxide synthase
Not normally expressed but can be induced by infection or cytokines
It accounts for the killing of microorganisms by macrophages
Vascular actions of NO
ACh needs NO to be a vasodilator
Relaxation if endothelium is intact
No effect or constriction if endothelium is damaged
But basal release of NO exerts tonic vasodilator influence.
Mechanism by which cGMP evokes relaxation
NO activates soluble GC
This converts GTP to cGMP.
cGMP plus PKG causes a reduction in intracellular calcium.
This reduces calcium sensitivity of contractile proteins and therefor vauses relaxation.
Blockage of NO (EDRF and NANC) nerves
Hb - binds to and inactivates NO with a stronger affinity than oxygen
ODQ/methylene blue - inhibits soluble guanylate cyclase by oxidation of the Fe2+ in haem moiety.
Potentiation of NO (EDRF & NANC) nerves
Zaprinest, sildenafil.
Selective inhibitors of cGMP-phosphodiesterase-5
Potentiates action of NO by slowing hydrolysis of the second messenger cGMP.
Properties of NO
Water soluble gas, higjly diffusable
Highly reactive free radical
Cannot be stored, freely crosses cell membranes
Must be synthesised when required from L-argenine.
Inhibitors of NOS isoforms
Ng- substituted analogues of L-argenine
- Ng-monomethyl-L-argenine (L-NMMA)
- Ng-nitro-L-argenine (L-NOARG)
- Ng-nitro-L-argeninemethylester (L-NAME)
NO physiological functions
Control of BP (NOS inhibitors increase BP)
Inhibit platelet aggregation and adhesion (antithrombotic)
Neurogenic vasodilation (cerebral and penile arteries)
Neurogenic relaxation (gut,respiratory and reproductive smooth muscle)
