37 - Nitric Oxide in the Vascular System Flashcards
What releases nitric oxide
GTN (Nitroglygerin)
Function of NO
Smooth muscle relaxation –> vasodilateion
What is EDRF
Nitric oxide
What can nitrous oxide be used for
Laughing gas
medication
What is entonox
Nitrous oxide 50%
Oxygen 50%
N20
What is entonox used for
Medical anaesthesia gas used in childbirth and emergency medicine
What does nitric oxide synthase od
NOS converts L-arginine —-> citrulline + NO using oxygen
isoforms of NOS
1) Brain
2) Macrophages
3) Vascular endothelium
What controls brain isoform of NOS
Intracellular calcium
What controls Macrophage isoform of NOS
- cytokines
What controls vascular endothelim isoform of NOS
Calcium
What causes synthesis of NO
Shear stress on wall caused by friction opens calcium channels –> calcium enters endothelial cells –> calmodulin activated by calcium –> activates eNOS
Co-factors required for NO synthesis
Biopterin H4
FMN
FAD
ACh, bradykinin, substance P - causes calcium to enter
What occurs when NO diffuses from endothelium to SM
NO activates guanylate cyclase
Converts GTP to cGMP
What does cGMP d
Makes smooth muscle relax - vasodilation to increase local blood flow
What do drugs inhibiting eNOS cause
Increase in resting BP
What does NO maintain
Normal BP
Low peripheral resistance
Function of NO in vascular system
Relaxes and dilates arteriolar smooth muscle
Prevents unwanted intravascular coagulation - Nitroglycerin –> NO
NO function in hypoxia
Aids in gas exchange between Hb and cells
into RBC –> reacts with oxyhaemoglobin –> nitroxyhaemoglobin which displaces oxygen from Hb and improves the delivery of oxygen to the hypoxic tissue
How does blood flow during exercise change to muscle, heart, kidnet, skin and brain
o Muscle x10 o Heart x3 o Kidney /2 o Skin x4 o Brain blood flow does not change
Cause of muscle blood flow changes during exercise
1) Vasoconstricion inactive muscle
2) Vasodilation in active muscle
What mediates vasoconstriction of arterioles
Alpha-1 receptors
Local vasodilators
NO
Adenosine
How is oxygen produced for NO synthesis in hypoxia (exercising)
Anaerobic resp –> lactate produced –> low pH converts nitrite –> HNO2 (nitrous acid) –> converted to NO using electron from ascorbic acid a reducing agent –> provides oxygen for later synthesis
eNOS activity in angina
Angina endothelium damaged –> eNOS reduced –> less dilation during exercise –> hypoxia –> Acidosis
What is persistant pulmonary hypertension of the Newborn
No reduction in pulmonary arterial resistance after first breath
Hypoxia - lungs not perfused
NO can be given to save
What causes decrease in pulmonary resistance with the first breath
Raises po2 in lungs –> NO synthesis –> relaxation of pulmonary vsmc –> dec PAR
Link between ventilation and perfusion
Low ventilation (PO2) Hypoxic constriction due to lack of NO (cannot be synthesised)
How much does cardiac output and pulmonary arterial pressure increase in exercise
CO - 3X
PAP - slightly
Resistance decreases (Diameter increases)
Why does diameter of arteries increase in exercise
Sympathetic activation of B2 receptors on bronchial smooth muscles
greater tidal volume - inc o2 conc
What affects brain blood flow
pH
Hypertension –> Low pCO2 –> alkaline blood –> reduces cerebral blood flow –> confusion and dizziness
What does acidity in the brain cause
Increase in blood flow to the brain
Resting brain blood flow
50ml/min/100gm
When reversible brain damage due to low blood flow
25ml/min/100g
When permanent brain damage
1/4 of resting brain blood flow
How does nitric oxide cause anticoagulation
Prevents leukocytes and platelets from adhering to the endothelium
What does low blood flow in veins cause
AFIB
DVT
Function of iNOS
Inducible NOS
- Induced by bacteria/toxins
Triggers toxic free radicals in the bacteria
Overproduction of iNOS
Uncontrolled local vasodilation - septic shock (organ failure and death)
Characteristics of SIR (Systemic inflammatory Response)
Fever Tachycardia Tachypnea Increased WBC (sepsis is SIR caused by infection)
Why is NO janus molecule
Good and bad points
