Pharmacology/physiology – Why does inhaled nitric oxide (NO) lower blood pressure only in the pulmonary circulation and not systemically?

Introduction:
Inhaled nitric oxide (iNO) is used clinically to selectively dilate pulmonary vessels, improving ventilation–perfusion matching. The selectivity arises from NO's chemistry and disposition rather than from unique pulmonary receptors. This question asks why the effect remains largely confined to lung tissue.

Given Data / Assumptions:

• NO is a gaseous signaling molecule produced by endothelial cells.
• It diffuses rapidly but has a very short biological half-life.
• Hemoglobin binds and inactivates NO within the bloodstream.

Concept / Approach:
When NO is inhaled, it reaches ventilated alveoli and diffuses into adjacent pulmonary vessels, where it activates soluble guanylate cyclase in smooth muscle to raise cGMP and cause relaxation. As soon as NO encounters hemoglobin in circulating blood, it is rapidly scavenged and converted to nitrate/nitrosylated species. This confines effective vasodilation to the pulmonary vasculature and prevents systemic hypotension.

Step-by-Step Solution:

Verification / Alternative check:
Clinical observation shows improved oxygenation and reduced pulmonary pressures without systemic hypotension at therapeutic iNO doses—consistent with rapid inactivation and localized delivery.

Why Other Options Are Wrong:

• Different signaling molecule elsewhere: systemic vessels also use NO among others.
• NO cannot cross membranes: it readily diffuses across membranes.
• Active pumping out of systemic vessels: not a recognized mechanism.

Common Pitfalls:
Assuming receptor selectivity explains localization; in fact, pharmacokinetics and hemoglobin scavenging dominate.

Final Answer:
Nitric oxide is extremely short-lived and inactivated rapidly, limiting it to the lungs where it is delivered