Characterization of Ca 2+ oscillations in pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension

A rise in cytosolic Ca 2+ ([Ca 2+ ] cyt ) in pulmonary artery smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and an important stimulus for PASMC proliferation, two major causes for elevated pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension (IPAH). The rise in [Ca 2+ ] cyt is mainly induced by Ca 2+ release and Ca 2+ influx. Under the resting conditions, we observed spontaneous and periodic increases in [Ca 2+ ] cyt , or Ca 2+ oscillations, in some (<5%) normal PASMC. Interestingly, 50% of IPAH‐PASMC showed spontaneous Ca 2+ oscillations. The amplitude of spontaneous Ca 2+ oscillations in IPAH‐PASMC was 5‐fold larger than in normal PASMC. Removal of extracellular Ca 2+ abolished the Ca 2+ oscillations in IPAH‐PASMC, while 10 μM La 3+ significantly decreased the amplitude and frequency of the Ca 2+ oscillations. Furthermore, application of OAG (100 μM), a membrane‐permeable diacylglycerol analogue, slightly increased [Ca 2+ ] cyt in 30% of normal PASMC, but elicited a large increase in [Ca 2+ ] cyt followed, sometimes, by Ca 2+ oscillations in most IPAH‐PASMC. In summary, human PASMC possess spontaneous and OAG‐induced Ca 2+ oscillations. The amplitude and frequency of the Ca 2+ oscillations are enhanced in IPAH‐PASMC, which may contribute to the sustained vasoconstriction and vascular remodeling in patients with IPAH. NIH grants: HL 066012 and HL 098053.