Expansion
Nitric oxide donation causes venodilatation, reducing preload and wall stress
Expansion
Nitrates are metabolised to nitric oxide, which activates guanylate cyclase, raises cyclic GMP and relaxes vascular smooth muscle.
Effects, in order of importance in angina:
- Venodilatation at low doses, reducing preload, ventricular volume and therefore wall stress and oxygen demand
- Coronary vasodilatation, particularly of large epicardial vessels and collaterals, redistributing flow to ischaemic subendocardium
- Arterial dilatation at higher doses, reducing afterload
Practical consequences:
- Contraindicated with phosphodiesterase-5 inhibitors such as sildenafil, since both act on the same pathway and profound hypotension can result
- Dangerous in right ventricular infarction and severe aortic stenosis, where the patient is preload dependent
- Tolerance develops with continuous exposure, so a nitrate-free interval of 8 to 12 hours a day is needed
- Headache is the commonest side effect, from cerebral vasodilatation