Introduction In the lungs of animal models for and patients with pulmonary arterial hypertension (PAH) increased numbers of mast cells have been demonstrated. We hypothesized that mast cell activation induces progression of pulmonary vascular remodeling. To test this hypothesis, we inhibited mast cell activation in a rat model of flow-associated PAH via treatment with a mast cell stabilizer (Cromolyn).
Methods Flow associated PAH was created in rats by injection with monocrotaline (60 mg/kg) followed by an abdominal aorto-caval shunt 1 week later. Rats were randomized into 2 groups: PAH (n = 13), PAH+ Cromolyn (PAH + Cromo n = 10 daily injections). Rats injected with saline followed by sham surgery served as controls (CON, n = 13). Three weeks later pulmonary hemodynamics, pulmonary vascular remodeling and number of mast cells in the lungs were assessed.
Results Compared to PAH, pulmonary vasculature of cromolyn-treated rats showed decreased medial wall thickness (3,9±0,4 mm in PAH vs. 2,1±0,5 mm in PAH + Cromo, p<0,01), occlusion (28,0±2,9 in PAH vs. 14,9±2,3 in PAH + Cromo, p<0,05), muscularization (24,1±2,2% in PAH vs. 12,9±2,8% in PAH + Cromo, p<0,05), and number of mast cells (0,9±0,14 in PAH vs. 0,6±0,2 in PAH + Cromo, p<0,1). Pulmonary arterial pressure and right ventricular hypertrophy were not significantly altered by Cromolyn treatment.
Conclusion In our model of flow-associated PAH in rats, we showed that inhibition of mast cell mobilization and activation using a mast cell stabilizer decreased pulmonary vascular remodeling. We speculate that attenuation of mast cell proliferation may be beneficial in flow-associated PAH.