Action of Nitric Oxide
Nitric oxide (NO) is a potent vasodilator that prevents platelet aggregation, with its actions primarily mediated through cyclic guanosine monophosphate (cGMP), not cyclic adenosine monophosphate. 1, 2
Primary Mechanism of Action
Nitric oxide functions through the following mechanisms:
Vasodilation: NO relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating it and increasing intracellular levels of cyclic guanosine monophosphate (cGMP), which leads to vasodilation 2
Platelet Inhibition: NO inhibits platelet adhesion, aggregation, and stimulates disaggregation of preformed platelet aggregates 3
Signal Transduction: The effects of NO are mediated through stimulation of guanylate cyclase and formation of cGMP, NOT through cyclic adenosine monophosphate 1, 2
Physiological Production and Storage
- NO is produced by three isoforms of nitric oxide synthase (NOS) that are present in multiple cell types 1
- NO is generated from L-arginine by nitric oxide synthase in endothelial cells 1
- NO is NOT normally stored in endothelial cells but rather produced on demand and released immediately 1
- The metabolic conversion of organic nitrates to nitric oxide occurs at or near the plasma membrane of vascular smooth muscle cells 1
Cardiovascular Effects
Nitric oxide provides several beneficial cardiovascular effects:
- Reduces right and left ventricular preload through peripheral vasodilation
- Decreases afterload through arterial vasodilation
- Improves myocardial oxygen supply-demand ratio
- Dilates coronary collateral vessels
- Reverses vasoconstriction of small coronary arteries distal to obstruction
- Reduces platelet aggregation 1
Clinical Applications
- Inhaled nitric oxide is used therapeutically in neonates with pulmonary hypertension 2
- NO donors are used in various cardiovascular conditions to exploit its vasodilatory and anti-platelet properties 4
- Deficient NO production or bioavailability is associated with various cardiovascular diseases including thrombosis, atherosclerosis, and hypertension 5
Important Considerations
- Excessive NO can lead to hypotension, vascular leakage, and disruption of cell metabolism 5
- NO has an extremely short half-life, limiting its direct therapeutic application 4
- The inhibition of platelet function by NO can result in prolonged bleeding time, which is an important consideration when administering inhaled NO to critically ill patients 3
Therefore, based on the evidence, the correct answer is B. Prevents platelets aggregation.