BACKGROUND: Chronic hypoxia induces lung vascular remodeling, which results in pulmonary hypertension. Vascular remodeling is associated with collagenolysis and activation of matrix metalloproteinases (MMPs). One of the possible sources of MMPs in hypoxic lung are mast cells. OBJECTIVE: The role of lung mast cell collagenolytic activity in hypoxic pulmonary hypertension was tested by the inhibitor of mast cell degranulation disodium cromoglycate (DSCG). METHODS: Rats were treated with DSCG in an early or later phase of isobaric hypoxia. Control groups were exposed to hypoxia only or to normoxia. Lung hemodynamics, muscularization and collagen metabolism in the walls of peripheral pulmonary vessels in the lungs were measured. RESULTS: DSCG applied at an early phase of exposure to hypoxia reduced the development of pulmonary hypertension, inhibited muscularization in peripheral pulmonary arteries and decreased the amount of collagen cleavage fragments in prealveolar vessels. CONCLUSIONS: Mast cell degranulation plays a role in the initiation of hypoxic pulmonary vascular remodeling.

Department of Physiology Charles University 2nd Medical School Prague Prague Czech Republic

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Mechanisms Controlling the Behavior of Vascular Smooth Muscle Cells in Hypoxic Pulmonary Hypertension