What is the mechanism of action of nitrates in relieving angina?

• A. They donate nitric oxide, causing vasodilation and reduced myocardial oxygen demand.
• B. They increase contractility by calcium sensitization.
• C. They inhibit HMG-CoA reductase.
• D. They activate PPAR-alpha.

Answer: (A)

Nitrates relieve angina by releasing nitric oxide, which activates soluble guanylate cyclase in vascular smooth muscle and raises cGMP. This causes relaxation, with veins dilating more than arteries. The resulting venodilation lowers venous return to the heart (preload), which reduces left ventricular end-diastolic pressure and wall stress. That decrease in wall tension lowers the heart’s oxygen demand, helping to relieve angina. Nitrates can also modestly dilate arteries and may improve coronary blood flow, but the dominant effect is reduced oxygen demand from decreased preload.

Other mechanisms mentioned—increasing contractility by calcium sensitization, inhibiting HMG-CoA reductase, or activating PPAR-alpha—do not describe how nitrates work; they pertain to inotropes or lipid-lowering drugs and aren’t how nitrates alleviate angina.