Effect of calcium-sensitive receptor on intracellular Ca2+ concentration in pulmonary arterial smooth muscle cells of hypoxia-induced persistent pulmonary hypertension in mice

Abstract

Objective To study the changes of intracellular calcium ion concentration in pulmonary artery smooth muscle cells (PASMCs) of hypoxic-induced persistent pulmonary hypertension (PPH) induced by calcium-sensitive receptor (CaSR) in a newborn mouse model. Method Ninety-six newborn C57BL/6 mice were randomly divided into control group, PPH group, PPH+ agonist group and PPH+ inhibitor group, with 24 mice in each group. The PPH model was induced by 12% oxygen for 14 days. In the beginning, intraperitoneal injection of CaSR agonist (GdCl3) and CaSR inhibitor (NPS2390) were performed to mice in PPH+ agonist group and PPH+ inhibitor group respectively daily. After 14 days of modeling, pulmonary artery smooth muscle cells (PASMCs) of all four groups were cultured in vitro. Changes of Ca2+ fluorescence intensity in PASMCs of the four groups were detected by laser confocal microscope continuously. Result The ratio of pulmonary small vascular wall thickness to the vascular diameter and right ventricle/left ventricular thickness in PPH group were greater than those in the control group [(21.1%±1.8%) vs.(27.0%±0.9%), (0.62±0.22) vs.(0.83±0.45)], the differences were statistically significant (P 0.05). Conclusion CaSR may be involved in the occurrence and development of hypoxic-induced PPH in neonatal mice by affecting the intracellular Ca2+ concentration in pulmonary artery smooth muscle cells. Key words: Hypertension pulmonary; Anoxia; Receptors, calcium-sensing; Myocytes, smooth muscle; Mice