Role of amlodipine in preventing and reversing monocrotaline-induced pulmonary arterial hypertension in rats

Abstract

Background: Amlodipine has been reported to be beneficial to improve vascular endothelial function, inhibit proliferation of vascular smooth muscle cells, and exert antioxidant actions. The present study was designed to examine the role of amlodipine in preventing and reversing monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. Methods: Rats were injected with 40mg/kg of MCT subcutaneously and randomized to either 6mg/kg/day of amlodipine in drinking water or placebo for 3 weeks. Animals treated with MCT and survived for 3 weeks were assigned to either amlodipine (6mg/kg/day) or placebo for next 3 weeks. Results: Amlodipine immediately following MCT markedly inhibited PAH (p < 0.01) with severe pulmonary vascular remodeling. The survival rate at 3 weeks after treatment was significantly increased in the amlodipine-treated group compared with the placebo group (90% vs 44%, p < 0.05). eNOS expression in the lung tissue was significantly reduced in the placebo group, but it was markedly improved after 3 weeks of amlodipine (p < 0.001). Late treatment with amlodipine did not palliate PAH nor improved survival. Conclusions: Amlodipine immediately after MCT injection inhibited development of PAH and improved survival in rats. These effects were associated with marked upregulation of eNOS in the lung tissue. In contrast, amlodipine failed to reverse established PAH. This study may provide an insight into therapeutic strategy of amlodipine in PAH.