Nitrates interact with which of the following?

• A. PDE5 inhibitors
• B. Guanylate cyclase inhibitors
• C. Both PDE5 inhibitors and guanylate cyclase inhibitors
• D. None

Answer: (C)

Nitrates act by releasing nitric oxide to stimulate soluble guanylate cyclase, which raises cyclic GMP in vascular smooth muscle and causes vasodilation. Any drug that alters the NO–cGMP pathway can interact with nitrates.

PDE5 inhibitors slow the breakdown of cGMP, so when combined with nitrates the cGMP rise is amplified, leading to excessive vasodilation and a dangerous drop in blood pressure. Similarly, drugs that influence guanylate cyclase activity affect the same signaling axis, so they can modify nitrate effects as well. Because both types of drugs modulate the NO–cGMP pathway, nitrates can interact with either, making the combination risky.