NO in Vascular system Flashcards
Entonox
Mix of nitrous oxide (N2O) and oxygen (50:50)
Medical anaesthesia gas
Nitric Oxide Synthase
NO Synthesis
Both oxidase + reductase domains
NO synthesis
Oxygen essential –> converts aa l-arginine to citrulline
H+ produced
Enhanced in alkali, inhibited in acidic
Prevented in hypoxic conditions
NO synthase location
Brain
Macrophages
Vascular endothelium
NOS type I
nNOS or bNOS
Central or peripheral and neuronal cells
Calcium dependent
NOS type II
iNOS
Most nucleated cells particularly macrophages
Independent of intracellular Ca 2+
Inducible in presence of inflammatory conditions
NOS type III
Endothelial NOS, eNOS
Vascular endothelial cells
Ca2+ dependent
NO synthesis in Vascular Endothelium
Shear stress on endothelial wall by moving blood flow
–> opens Ca2+ channels
Ca2+ enters endothelium
Ca2+ binds to calmodulin
Calmodulin activates eNOS
NO diffuses from endothelium into surrounding smooth muscle + activates guanylate cyclase
–> converts GTP–>cGMP (makes muscles relax)
cGMP acts through 3 main groups of cellular targets
cGMP-dependent protein kinases (PKGs)
cGMP-gated cation channels
Phosphodiesterases (PDEs)
cGMP
inhibits contraction
makes muscle relax
NO Function in Vascular system
NO relaxes and dilates arteriolar smooth muscle
NO prevents unwanted intravascular coagulation
NO in lungs
relaxes bronchial smooth muscle
NO + Gas exchange
NO diffuses into blood + smooth muscle during hypoxia
In erythrocyte, reacts with oxyhaemoglobin to form nitrosohaemoglobin
–> displaces O2 from haemoglobin
–> NO IMPROVES O2 DELIVERY IN HYPOXIC TISSUE
Blood flow in Active muscles during exercise
Increases 10x
Coronary blood flow during exercise
increases 3x
Kidney blood flow during exercise
Decreases by nearly half
Skin blood flow during exercise
Increases 4x
Brain blood flow during exercise
Does not change
Skeletal muscle blood flow during exercise
SNS produces general vasoconstriction of arterioles in muscle (mediated by alpha 1 adrenoreceptors)
–> reduces local muscle blood flow
Muscle which is exercising vasodilates
–> overcomes global symp. vasoconstrictor tone
–> increases local BF by opening arterioles
Local vasodilators
Adenosine
NO- more important than adenosine in vasodilation in hypoxic muscle
Acidosis
Triggers vasodilation in exercising muscle
By lactic acid
NO storage
Can’t be stored in cells or organelles as is gas
Constantly synthesised at low levels in resting vascular endothelium
NO converted to nitrate –> stored in endothelium –> when hypoxia, converted back
Nitroglycerin (GTN)
Essential drug for treating angina + MIs
Dilates coronary arteries
GTN –> nitrate in circulation
Dipyridamole
Vasodilator
Increases adenosine conc. in blood
Increases size of blood vessels - BUT doesn’t affect atheroma blockage
Nitrite –> NO
Hypoxic and environment
Persistent pulmonary hypertension of the newborn (PPHN)
Raise pulmonary vascular resistance
–> NO to inspired gas dramatically improves lung function in these children
Foetus pulmonary arterioles
Resting state is constriction
First breath - O2 rises + rapid synthesis of NO –> relaxation vascular smooth muscle –> vasodilation
Pulmonary arterial resistance decreases in exercise
Pulmonary arterial walls thin
Increased flow through pulmonary arterioles may increase NO synthesis
Symp NS acts on beta 2 receptors on bronchial smooth muscle –> relaxes them + increases bronchial diameter
eNOS in pulmonary endothelium is highly sensitive to O2 partial pressure –> when O2 partial pressure rises, so does NO production
No and coagulation
Base release of NO helps prevent leukocytes + platelets from adhering to surface of endothelium
NO + digestive system
Nitrates in vegetables converted to nitrated by enzymes in saliva + nitrites enter the stomach
Acidic stomach= nitrite + ascorbic acid –> NO
NO in acidic conditions is bactericidal + kills harmful bacteria in food
Nitrosamines
Carcinogenic
Nitrites converted into nitrosamines in SI
