Trigger 4: Therapeutics using NO and inorganic nitrate supplementation Flashcards
give an example of an organic nitrate
isosorbide mononitrate
give an example of an inorganic nitrate
nitrate ion
organic nitrates as vasodilators
- medicinally synthesised products
- very effective and quick vasodilators
the body alone cannot process organic nitrates, what does it need
symbiont bacteria
inorganic nitrate are produced
endogenously and also taken in from diet
inorganic nitrates have a
slow vasodilatory effect
NO donors are
organic
example of indirect NO donors
Nitroglycerin, isosorbide mononitrate
example of direct NO donor
sydnonimines
molsidomine
how do indirect NO donors work
activate soluble guanylate cyclase and reduce Ca2+ uptake –> smooth muscle relaation
how do direct NO donors work
activate soluble equaniylate cycle.
lowers ICAM-1 production preventing monocyte infiltration
opens ATP-sensitie potassium channels (casodilator
benefits of indirect NO donors
- increased survival in patients with heart failure
- decreases progression of lesion formation, endothelial dysfunction and LDL oxidation
- lowers BP
- reduces atherosclerosis
- Anti-plateles aggregation
benefits of direct NO donors
- no tolerance of NO as thiol independent
- reduces BP
- reduces atherosclerosis
- reduces inflammation
- anti-platelet aggregation
limitation of indirect NO donors
Tolerance of NO
- increased production of superoxide anion by the endothelium produces NO that is inactivated = loss of responsiveness
- tissue sulfhydryl groups (-SH) required for expression of vasodilator action of organic nitrates (reacting with nitrates to release NO) – repeated administration would lead to the depletion or to the oxidation of tissue thiols
who are NO donors for
angina patients
what are inorganic nitrate supplements
NO3- in pure form- no carbon
what may NO3- come bonded with
K or NA
- although unlikely to be with Na+ as most patients will be on a low Na+ diet anyway.
how do inorganic nitrates work
same as if you were eating nitrate from foods such as beetroot
when are inorganic nitrates used
Same as organic nitrates, in the presence of angina:
- hypertension
- post-MI and other CVD.
benefits of inorganic nitrate supplementation
- reduces systolic BP
- endothelial protective effect
- reduces oxygen cost of exercise
- protects against metabolic syndromes
- protects against schema repression injury
reducing oxygen cost of exercise means that
performance is enhanced–> improved endurance
harms of inorganic nitrate supp
- cancer
- methemoglobin
cancer and inorganic supp
nitrate has the potential to form carcinogenic nitrosamines (implication not fully understood)
methemoglobin andinorganic supp
nitrite is reduced to NO which oxidises haemoglobin
Excessive hemoglobin in Fe3+ oxidized state is unable to bind and deliver O2 to tissues
