Effects of nitric oxide on the vascular system
Regulation of eNOS
Medications
Effects of impaired NO production
Endothelial dependent hyperpolarisation
Influence of shear stress
VASCULAR SYSTEM 2 - VASODILATION
NITRIC OXIDE
• widely produced in the body - released by endothelial layer - specific to vasculature
• transmitter in the central and peripheral nervous system
• short half life - 10-60s
• imbalance of NO production is implicated in many clinical conditions
◦ hypertension/atherogenesis
• actions of NO
◦ Immune function
▪ Inhibit platelet adhesion and aggregation
▪ Inhibit monocyte adhesion and migration
▪ Inhibit smc and fibroblast proliferation
▪ (Host defence: Contributes to cytotoxic killing mechanisms of immune
cells)
◦ vascular function
▪ induces SMC relaxation via activation of cGMP dependent protein kinases in
smc
• synthesis and breakdown of NO
◦ Synthesised by the oxidation of L-Arginine
◦ oxidised to L-citruline + NO
◦ Cofactors: NADPH, BH4, oxygen, Calmodulin
• NO is short acting
◦ oxidised to nitrate/nitrite
▪ Oxygenated haemoglobin
▪ Molecular Oxygen
▪ Superoxide anions
◦ Forms nitrosothiols – release NO over a longer time period
• Synthesis and breakdown of NO:
• Nitric oxide synthases: 3 isoforms
◦ eNOS - endothelial
◦ nNOS - neuronal
◦ iNOS - inducible NOS - in disease states
• Basal production of NO - low levels needed to relax the vessels slightly to
prevent hypertension
• Caveolae - cholestorol rich regions in bilayer
◦ eNOS localised in Caveolae (Cholesterol rich)
◦ Associates with Caveolin-1 protein
▪ (reversible interaction)
, ▪ (inhibitory)
• Action on smc:
◦ NO binds to soluble guanylate cyclase in smc leading to activation of cGMP
◦ cGMP activates cGMP-dependent protein kinases
◦ Ca sequestration and reduced intracellular Ca
◦ Smc relaxation
• Action inhibited by substrate analogues
◦ Eg. L-NMMA (N-monomethyl Larginine
◦ Eg. L-NAME (N-nitro L-arginine methyl ester)
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller finlaybeaton. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for £4.48. You're not tied to anything after your purchase.
