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Previously we demonstrated that both hypoxia inducible factor-1 (HIF-1) and bone morphogenetic protein-4 (BMP4) up-regulate transient receptor potential canonical (TRPC) 1 and TRPC6, resulting in increased basal intracellular Ca²⁺ concentration ([Ca²⁺]_i) in pulmonary arterial smooth muscle cells (PASMCs), driving development of chronic hypoxia (CH)-induced pulmonary hypertension (CHPH). This study aims to determine whether HIF-1 regulates BMP4, and whether BMP4 mediates TRPC and basal [Ca²⁺]_i increases in hypoxic PASMCs.

The level of BMP4 mature protein was increased for ∼183% in distal pulmonary arterial smooth muscle (PA) from CH (10% O₂ for 21 days; CH) exposed rats, and 143% in PASMCs cultured under prolonged hypoxia (4% O₂ for 60 h). In rat PASMCs, HIF-1α overexpression up-regulated, whereas HIF-1α …