Lesson 1

Control of Airway Diameter

• Airway Radius Contribution: Radius most significantly affects airflow resistance.

• Physiologic Regulators of Airway Diameter:

  • PNS (Vagus Nerve): Leads to bronchoconstriction, reducing airflow.
  • Mast Cells & Non-Cholinergic PNS: Induces bronchoconstriction, further reducing airflow.
  • Non-Cholinergic PNS (Nitric Oxide): Promotes bronchodilation, improving airflow.
  • SNS (Circulating Catecholamines): Promotes bronchodilation, improving airflow.

• Mechanisms:

  • Bronchoconstriction:
  • M3 receptor (coupled to Gq protein) activated, stimulating phospholipase C (PLC) and inositol triphosphate (IP3), increasing intracellular Ca²⁺ and promoting contraction.
  • Bronchodilation:
  • ẞ2 receptors activated by circulating catecholamines, stimulating adenylate cyclase, increasing cAMP, reducing Ca²⁺ release, thus inducing relaxation.

• Important Chemicals:

  • Nitric Oxide: Potent smooth muscle relaxant, stimulates cGMP production for bronchodilation.
  • Other mediators from mast cells include histamine, leukotrienes, prostaglandins affecting bronchoconstriction.

• Pathway Summary:

  • Bronchoconstriction (from PNS activation): Ach → M3 → Gq → PLC → IP3 → Ca²⁺ release → contraction.
  • Bronchodilation (from SNS activation): Catecholamines → ẞ2 → Gs → Adenylate Cyclase → cAMP → PKA → reduces Ca²⁺ → relaxation.