Which of the following is the primary mechanism by which histamine increases vascular permeability in acute inflammation?

Explanation

## Histamine and Vascular Permeability **Key Point:** Histamine is a preformed mediator stored in mast cell granules that acts on H1 and H2 receptors on endothelial cells, causing them to contract and create intercellular gaps through which fluid and proteins leak into tissue. ### Mechanism of Action Histamine binds to endothelial cell receptors and triggers: 1. Cytoskeletal contraction via actin-myosin interactions 2. Widening of intercellular junctions (paracellular route) 3. Increased transudation of plasma proteins and fluid This is a **reversible and immediate** response (within seconds to minutes), making histamine the primary mediator of acute vascular permeability changes in the early phase of inflammation. **High-Yield:** Histamine acts on **post-capillary venules**, not arterioles or capillaries. The increased permeability is **transient** (15–30 minutes) because histamine is rapidly degraded by histaminase and monoamine oxidase. ### Other Mediators Causing Permeability | Mediator | Mechanism | Onset | Duration | |----------|-----------|-------|----------| | Histamine | Endothelial contraction | Immediate | 15–30 min | | Bradykinin | Endothelial contraction + gap formation | Immediate | 15–30 min | | Leukotrienes (C4, D4, E4) | Endothelial contraction | Delayed | Prolonged | | TNF-α, IL-1 | Endothelial injury + adhesion molecule upregulation | Delayed | Hours | | Complement (C3a, C5a) | Mast cell degranulation + direct endothelial effects | Immediate | Variable | **Clinical Pearl:** Antihistamines (H1 blockers like diphenhydramine) are effective in acute allergic reactions because they block histamine-mediated permeability; however, they are ineffective against bradykinin or complement-mediated responses.