Which class of therapy for pulmonary arterial hypertension increases cGMP to promote vasodilation and has interactions with nitrates?

• A. Endothelin receptor antagonists
• B. Phosphodiesterase-5 inhibitors
• C. Prostacyclin analogs
• D. Guanylate cyclase stimulators

Answer: (B)

Phosphodiesterase-5 inhibitors increase cGMP by blocking its breakdown in pulmonary vascular smooth muscle, which promotes relaxation and vasodilation, lowering pulmonary vascular resistance. A key clinical point is their interaction with nitrates: nitrates raise NO and boost cGMP production, so combining them with PDE-5 inhibitors can cause a dangerous drop in blood pressure due to excessive cGMP. This mechanism—preserving cGMP to achieve vasodilation with a known nitrate interaction—makes this class the best fit. Endothelin receptor antagonists work by blocking endothelin-1–mediated vasoconstriction, prostacyclin analogs act mainly through cAMP pathways, and guanylate cyclase stimulators also raise cGMP but via a different direct mechanism with their own nitrate cautions.