Nitric oxide

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spare electron which makes it highly reactive and short lived

body has to be able to synthesise it on demand as it can't be stored

*stress and agonist will stimulate NO = important mediator

Function:

control of blood pressure

neurogenic relaxation of smooth muscle

co transmitters in ANS

role in killing bacteria/fungi/viruses/parasites invading host cell

When things go wrong:

- septic shock - in response to blood infection = massive production of NO, reacts with super oxide anions and produces peroxynitrite which is very damaging and detrimental to health

Nitric oxide synthase (NOS) - enzymes central to NO biosynthesis

3 isoforms of Nitric oxide:

1. eNOS = endothelial, present also in cardiomyocytes + airways

Vasodilation

inhibition of platelet adhesion and aggregation

stops clots forming - help to maintain blood flow

inhibit smooth muscle proliferation - protects against development of atheroma - which can cause cardiovascular disease by restricting blood vessels

*endothelium is responsible for Ach response - releases vasodilator substance which relaxes underlying muscle

2. nNOS = neuronal, nerve terminals and CNS (act as co transmitter)

Commonly found in CNS

widespread action

NO will stimulate sGC - depending on target cell will see different effects

Non adrenergic, non cholinergic (NANC) transmitter

3. iNOS = inducible - not always present, stimulated to invading pathogens/bacteria (found in macrophages, neutrophils and cardiovascular system. Enzyme is produced in large quantities and huge quantities of NO

host defence

vascular smooth muscle

used by body to kill invading pathogens

can result in sepsis

*Glucocorticoids inhibit synthesis of iNOS = prevent progression of septic shock

NO - relax any underlying smooth muscle cell

Nitrate - bypass endothelial part of pathway and spontaneously breakdown - rapid and short lived effects, quickly alleviate symptoms (acute angina)