4 - nitric oxide system (disease and therapeutics)

Question 1

why might we have excess nitric oxide

Answer 1

septic and cardiogenic shock
- cause hypotension (NO lowers BP)

dermatological conditions such as psoriasis
- NO is a vasodilator and causes the redness on the skin

neurologies e.g. migraines
- NO increases cerebral blood flow

cancer
- promotes tumour growth by increasing blood supply

Question 2

important of NOS inhibitor if patient is in shock

Answer 2

shock causes hypotension
NOS inhibitors would revert this
and increase blood pressure of patient

Question 3

side effects of nitric oxide inhibition therapies

Answer 3

damaging to those with cv diseases

Question 4

role of NO during ischemic events

Answer 4

NO is cardio-protective
provides increased blood/oxygen supply
causes vasodilation

Question 5

role of NO inhibitors in chronic kidney disease

Answer 5

causes vasoconstriction
increase in blood pressure
endothelial dysfunction

Question 6

2 endogenous NOS inhibitors

Answer 6

ADMA

L-NMMA

Question 7

ADMA

Answer 7

endogenous non-competitive NOS inhibitor

potent

Question 8

example of NO scavenger

Answer 8

haemaglobin

Question 9

conditions associated with NO deficiency

Answer 9

hypertension

congenital abnormalities, including achalasia cardia, hypertrophic pyloric stenosis, and Hirschsprung disease

Chronic kidney disease

Question 10

insufficient nitric oxide in the skin can cause….

Answer 10

psoriasis

by promoting cell proliferation and reducing differentiation of skin cells.

Question 11

how is nitric oxide related to diabetes

Answer 11

pancreatic beta cells produce NO which may cause apoptosis

damage to beta cells is a cause of type 1 diabetes.

Question 12

what are organic nitrates used to treat

Answer 12

heart failure (myocardial infarction)
angina

Question 13

what are nitrodilators

Answer 13

drugs that mimic the actions of endogenous NO by releasing NO or forming NO within tissues

Question 14

how do nitrodilators work

Answer 14

NO produced acts directly on the vascular smooth muscle to cause relaxation and therefore serve as endothelial-independent vasodilators.

Question 15

how are inorganic nitrate drugs taken

Answer 15

orally –> under the tongue

Question 16

disadvantage to inorganic nitrate drugs

Answer 16

tolerance builds up after frequent use which reduces efficacy

need period of time not exposed to drug so nitrate can be liberated

endothelial dysfunction caused

Question 17

outline experiment showing effect of oral nitrate on plasma nitrite and BP

Answer 17

control vs beetroot juice
oral nitrate decreases systolic BP
changes mirrored in plasma nitrite

Question 18

reasons why inorganic nitrate supplementation could be useful?

Answer 18

1 - decreases BP
2 - protects against IR (ischemia reperfusion) injury
3 - improves ability to exercise
4 - protects against metabolic syndrome

Question 19

how does NO effect ability to exercise

Answer 19

reduces amount of O2 needed per workload

increases endurance and efficiency of O2 use

Question 20

haemoglobinemia

Answer 20

excess of heamoglobin in the blood plasma

Question 21

what is the DASH diet

Answer 21

low salt diet
reduce dairy and fats
increase fruit and veg intake

try and eat 20mmol nitrate per day to reduce BP

Question 22

blue babies

Answer 22

caused by methaemoglobinemia

excess NO oxidises haemoglobin to methaemoglobin

babies do not have methaemaglobin reductase so oxygen is not released to tissues

Question 23

met-haemoglobin reductase

Answer 23

reduces methaemaglobin to haemaglobin so oxygen can be released

not found in infants

Question 24

nitric oxide affect on haemaglobin

Answer 24

oxides Fe2+ to Fe3+

high affinity for oxygen

low carrying capacity –> does not release in tissues

Question 25

disadvatnages to supplementing water supply with nitrates

Answer 25

can cause methaemoglobinema --> blue babies who cannot deliver oxygen to tissues

Question 26

why do babies growing up on rural/agricultural land suffer from blue baby sydrome

Answer 26

bacterial contamination of the water converts nitrates (safe) from fertilizers into nitrites (unsafe)

Question 27

why do NO drugs need a higher dose to cause arteriolar dilation

Answer 27

NO has less effect on arteries than veins

Question 28

differences between organic and inorganic nitrates

Answer 28

bacteria and the body process them differently

Question 29

nitric oxide donor therapeutics

Answer 29

attach drugs to NSAIDs (e..g ibruprofen)

Question 30

what kind of bacteria convert nitrate to nitrite

Answer 30

facultative anaerobes

Question 31

why are NOS enzymes unusual

Answer 31

they require co-factors | e.g. FAD, BH4

Question 32

2 examples of co-factors in NOS signalling pathway

Answer 32

FAD BH4 FMN NADPH

Question 33

why is iNOS calcium insensitive

Answer 33

binds tightly to calmodulin

Question 34

cGMP

Answer 34

cyclic GMP inhibits Ca2+ influx into the cell --> smooth muscle relaxation

Question 35

nitrate/nitrite concentrations in people with cv risk factors

Answer 35

low plasma nitrite (NO2-) | high plasma nitrate (NO3-)

Question 36

mechanism behind viagra

Answer 36

viagra inhibits breakdown of cGMP therefore NO-mediated vasodilation is enhances more blood flow can reach penis treats erectile dysfunction

Question 37

effect of superoxide anion

Answer 37

reduces bioavailability of NO | has higher affinty for NO

Question 38

nitroglycerin

Answer 38

nitrate drug taken to reduce angina (chest pain)

Question 39

delivery of nitroglycerin

Answer 39

tablet spray patch

Question 40

nitroglycerin mechanism

Answer 40

converted to NO in the body | acts as a vasodilator

Question 41

give two examples of nitrate vasodilators

Answer 41

``` Glyceryl trinitrate (nitroglycerin) isosorbide mononitrate ```

Question 42

what causes decreased bioavailability of NO in cv disease

Answer 42

endothelial dysfunction