In hypoxic pulmonary vasoconstriction (HPV), the sensor for alveolar hypoxia is located in which cell type, and what is the proposed effector mechanism?

• A Alveolar type II pneumocytes; reduced surfactant production causes alveolar collapse and mechanical stimulation of smooth muscle
• B Pulmonary neuroepithelial bodies; serotonin release causes adjacent smooth muscle contraction via 5-HT2 receptors
• C Hypoxia-inducible factor-1 (HIF-1) in endothelial cells; upregulates ET-1 gene transcription within minutes
• D Pulmonary arterial smooth muscle cells; mitochondrial generation of reactive oxygen species (ROS) or H₂O₂ inhibits voltage-gated K⁺ channels (Kv), causing depolarization and L-type Ca²⁺ channel activation ✓

Explanation

HPV is an intrinsic response of pulmonary arterial smooth muscle cells (PASMCs) to alveolar hypoxia, independent of neural or humoral input. Low PO₂ alters mitochondrial electron transport, changing the NADH/NAD⁺ ratio and ROS production. Increased H₂O₂ (or decreased H₂O₂, theories vary) inhibits voltage-gated K⁺ channels (notably Kv1.5/Kv2.1), causing membrane depolarization. This opens L-type Ca²⁺ channels, raising intracellular Ca²⁺ and triggering vasoconstriction. HIF-1 transcriptional effects operate over hours, not minutes, and are not the acute sensor mechanism.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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