Flashcards in Nitric Oxide in the Vascular System Deck (22)
What type of molecule is nitric oxide?
A free radical (there is an unpaired electron on the outside of the molecule)
What are free radicals? Give an example.
Molecules with an unpaired electron which therefore seek another electron from another molecule so that they can combine to form a more stable compound, and are therefore oxidising agents. Superoxide (O2-) is a free radical found in the body
How many forms of nitric oxide synthase are there?
Three, NOS type I, II and III
Describe the location and action of nitric oxide type I
NOS type I is found in the brain and is present in the central and peripheral neuronal cells. This type of NOS is calcium-dependent
Describe the location and action of nitric oxide type II
NOS type II is also known as inducible NOS (iNOS) as it is found in macrophages and can be induced by the presence of inflammatory cytokines and action is independent of calcium levels.
Describe the location and action of nitric oxide type III
NOS type III is found in the vascular endothelium and it is calcium-dependent
Which nitric oxide synthase enzymes are calcium-dependent?
NOS I and NOS III, but NOS II is calcium-independent
Explain the process of nitric oxide synthesis
In endothelial cells, the 'shear stress' caused by blood flow causes calcium channels to open so Ca2+ enters the endothelial cell. This calcium influx activates calmodulin which then activates the eNOS (within the presence of many cofactors) which then converts L-arginine into nitric oxide and citrulline.
Explain how nitric oxide can lead to vasodilation
After nitric oxide has been produced in the endothelial cell it diffuses into the smooth muscle of the tunica media of the blood vessel where it activates guanylate cyclase (GC) which then converts GTP into cGMP which then acts directly to relax the vascular smooth muscle
Outline the vascular actions of endothelial nitric oxide
Direct vasodilation, anti-thrombotic effect as it inhibits platelet adhesion to endothelium, anti-inflammatory effect as it inhibits leukocyte adhesion to the endothelium and anti-proliferative effect as it inhibits smooth muscle hyperplasia
Explain why resting blood pressure would rise if eNOS was inhibited in the whole body
NO synthesis balances the vasoconstrictor effects of noradrenaline and angiotensin on the blood vessels in order to maintain a healthy bP
How is nitric oxide involved in increasing coronary collateral circulation?
Nitric oxide increases coronary blood flow by opening up collaterals in the coronary circulation which acts to supplement the endogenous NO release and bypass arteries that are stenosed by atheromatous plaques
How does nitric oxide aid in oxygen delivery?
Nitric oxide that is released from vascular endothelium can also diffuse into the blood (as well as smooth muscle), and in the RBC it reacts with oxyhaemoglobin to form nitroshaemoglobin which displaces the oxygen from the haemoglobin in the RBC and therefore makes it readily available to diffuse into the tissues. (oxyhaemoglobin + NO oxygen + nitroshaemoglobin)
Explain how nitric oxide is involved in 'blood shunting' during exercise
During exercise, the sympathetic nervous system produces a general vasoconstriction of the arterioles in muscles during exercise (mediated by alpha-1 receptors). This tends to reduce local muscle blood flow. However, the muscles which are activity exercising/respiring will release powerful local chemical factors such as nitric oxide and adenosine, which counteract the sympathetic tonal vasoconstriction and instead lead to a local vasodilation.
How is nitric oxide synthesised at the beginning of exercise when oxygen levels are depleted?
Normal synthesis of NO cannot occur due to hypoxia (as oxygen stores become depleted quickly) and therefore muscles contain a store of nitrite (NO2-) which becomes nitrous acid due to anaerobic respiration (lactate production) and then the nitrous acid is converted to nitrous acid by combining the acid with an electron from ascorbic acid; this NO will hen diffuse into the smooth muscle of the tunica media and cause activation of GC --> GTP to cGMP --> vasodilation
What is persistent pulmonary hypertension of the newborn (PPHN)?
This is a condition whereby a new-born doesn’t experience a reduction in the pulmonary arterial resistance following the first breath and as a result they suffer from hypoxia as their lungs aren’t properly perfused and therefore they cannot collect oxygen
How may persistent pulmonary hypertension of the newborn (PPHN) be treated?
Adding nitric oxide to the inspired gas given dramatically improves the lung function in these children and can be life-saving
How is nitric oxide involved in shunting away from poorly perfused regions of lung?
In adults, nitric oxide is continuously produced in the healthy lung in order to maintain a low resistance in the pulmonary arterioles, however, if a lung region becomes hypoxic, nitric oxide production is reduced and therefore the arteriole constricts. Therefore, if ventilation (pressure of oxygen) is low, then hypoxic vasoconstriction will occur due to the reduced synthesis of nitric oxide.
Explain how nitric oxide is involved in the reduction of pulmonary arterial resistance during exercise
• During exercise the sympathetic nervous system acts on beta-2 receptors on the bronchial smooth muscle to relax them and increase bronchial diameter, and therefore this increased diameter alongside a greater tidal volume leads to an increased oxygen concentration in the alveoli
• The eNOS in the pulmonary endothelium is sensitive to the oxygen partial pressure and therefore when it rises, so does the production of nitric oxide
• The drop in pulmonary resistance during exercise is therefore mainly due to an increased pulmonary synthesis of nitric oxide
What factors slow cerebral blood flow?
Alkalosis and inhibition of bNOS
What factors promote cerebral blood flow?
Brain pH acidosis and increased local neuronal activity