NO in cardiovascular system Flashcards
What conversion reaction forms nitric oxide
L-arginine–> citrulline
What enzyme is used to form nitric oxide
Nitric oxide synthase
Apart from the enzyme, what else is required for synthesis of nitric oxide
Oxygen
Name 3 relevant isoforms of nitric oxide
Type 1= brain NOS= bNOS
Type 2= iNOS
Type 3= endothelialNOS= eNOS
Which 2 isoforms of NO are most closely related
bNOS and eNOS
Which 2 isoforms of NO are calcium dependent
bNOS and eNOS
What cells use bNOS
central and peripheral neuronal cells
What cells use iNOS
Most nucleated cells especially macrophages
What cells use eNOS
Vascular and endothelial cells
What is the main regulatory factors in NO synthesis
flowing blood
How does flowing blood activate NO synthesis
- Shear stress of endothelial wall causes opening of Ca2+ channels allowing calcium into endothelium
- This activates calmodulin
- This activates eNOS
What cofactors are required in the synthesis of NO
H4, FMN and FAD
How can acetylcholine activate NO
Binds to Ach receptor on endothelium
Allows calcium entry
How does NO work to stop cell contractions
- NO diffuses into surrounding smooth muscle
- Activates guanylate cyclase
- This converts guanosine triphosphate– cyclic guanosine monophosphate
- This removes calcium and open potassium channels
Main 2 functions of NO
- Relaxes and dilates anterior smooth muscle lowering vascular resistance
- Prevents unwanted intravascular coagulation opposes effect of noradrenaline and angiotensin
How does eNOS aid in gas exchange between haemoglobin and cells
NO released from vascular endothelium during period of local hypoxia, diffuses into blood as well as smooth muscle
In red cells, reacts with oxyhaemoglobin to form nitrosohaemoglobin
Displaces oxygen from haemoglobin improving delivery of o2 to hypoxic tissues
How is blood redistribution achieved during exercise
Sympathetic nervous system causes systemic vasoconstriction
Exercising muscles release local dilators which can overcome constriction
Therefore exercising muscles dilated and inactive ones constricted
What local vasodilators are used by exercising muscles during exercise
NO and adenosine
What triggers vasodilation during exercise
Lactic acid causes acidosis
What is the effect of acidosis on coronary circulation
Diameter of coronary arteries and number of open arterioles (collaterals)
Can NO be synthesised in hypoxic tissues
No- requires oxygen
In what form is NO stored when not immediately needed
Nitrite (NO2)
What 2 equations allow storage on NO as nitrite
NO+ H20—> HNO2 + H+ + e-
HNO2—» H+ + NO2
Where does the first equation that allows conversion of NO to nitrite occur
Pulmonary venous blood
When is nitrite converted back to NO
Hypoxic conditions
What is glycerol trinitrate used for? Brief mechanism
Drug used for heart attacks
Nitrite to NO
What effect does NO have on pulmonary arterial pressure
Low
What is effect of NO on the lungs during hypoxia
Production of NO reduced- constriction
How does cardiac output change during exercise
3 fold increase
How is increase of pulmonary blood flow during exercise achieved
Decreasing pulmonary resistance because distension of thin arteriolar walls leads to more NO synthesis
Also relaxation of bronchial smooth muscle by B2 receptors
How does NO aid in anticoagulation
NO release from vascular endothelium preventing adhesion of leukocytes and platelets
