What is the mechanism of action of nitroglycerin?

Correct answer: C. It is metabolised to nitric oxide, which activates guanylyl cyclase and raises cyclic GMP

• A. Beta-1 antagonism is the mechanism of the beta blockers such as metoprolol and atenolol.
• B. L-type calcium channel blockade is the mechanism of the calcium channel blockers such as amlodipine, nifedipine, diltiazem and verapamil.
• C. CORRECT. Nitroglycerin is a NITRIC OXIDE donor. It is denitrated in vascular smooth muscle to NITRIC OXIDE, which activates SOLUBLE GUANYLYL CYCLASE, raising intracellular cyclic GMP. Cyclic GMP activates protein kinase G, dephosphorylating myosin light chains and relaxing smooth muscle. The effect is greatest on VEINS, so the dominant action is reduced PRELOAD — less venous return, less ventricular wall tension, less myocardial oxygen demand. That, more than coronary dilatation, is how it relieves angina.
• D. Nitroglycerin acts on the guanylyl cyclase–cGMP pathway, not the adenylyl cyclase–cAMP pathway.

Note: ⚠️ Chairside safety point: nitroglycerin is ABSOLUTELY CONTRAINDICATED with PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) taken within the preceding 24–48 hours. Both act on the same cGMP pathway and the combination can cause catastrophic, refractory hypotension. Always ask before administering nitroglycerin for chest pain.