IHD and nitric oxide Flashcards
define myocardial ischaemia?
myocardial oxygen demand exceeds supply due to narrowing of arteries
what happens when ATP is produced non-aerobically?
lactic acid produced
dissociates into H+ and lactate
low ATP and high H+ ions cause abnormal ventricular contraction
what does persistent ischaemia cause?
lactic acidosis - inhibits glycolysis
infarction
consequences of myocardial ATP deficiency?
- impairment of ventricular systolic pumping
- decreased compliance of myocardium during diastole
- pulmonary congestion and dyspnoea
what does impairment of ventricular systole cause?
increased load, diminished contractility
reduced ejection fraction
what does decreased compliance during diastole cause?
hypertrophy of myocardium - thickening
impaired diastolic filing
what does congestion and dyspnoea cause?
backflow and cardiac failure
2 principles of treatment options?
1) reduce O2 demand (myocardial consumption) by decreasing cardiac work
2) increase O2 supply by improving coronary blood flow
what acts as a vasocostrictor?
O2
what acts as a vasodilator?
bradykinin, histamine, Ach
process of smooth muscle relaxation with nitric oxide?
1- Ach binding to to G protein receptors causing IP3 production
2- IP3 releases Ca2+ from ER
3- Ca2+ and calmodulin complex stimulates NO synthase to produce NO
4- NO diffuses into smooth muscle cells
5- activates guanylyl cyclase to make cGMP
6- activates PKG
7- activates myosin light chain phosphatase MLCP
8 - dephosphorylation of myosin light chains cause muscle relaxation
what is the dual action of nicorandil?
NO donor (blood flow maximised)
Opens ATP-dependent potassium channels (arterial dilation)
