Effects of calcium-sensitive receptors on 11β-hydroxysteroid dehydrogenase type 2 and cortisol in neonatal mice with persistent pulmonary hypertension / 中国当代儿科杂志

OBJECTIVE@#To investigate the effects of calcium-sensitive receptors (CaSR) on the expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) and cortisol concentration in a neonatal mouse model of persistent pulmonary hypertension (PPH).@*METHODS@#Fifty-six newborn C57BL/6 mice were randomly divided into a control group (n=14), a PPH group (n=14), an agonist group (n=14), and an inhibitor group (n=14). The mice in the PPH, agonist, and inhibitor groups were exposed to a 12% oxygen concentration, and the agonist group and inhibitor group were given CaSR agonist (GdCl3, 16 mg/kg) and CaSR antagonist (NPS2390, 1 mg/kg) intraperitoneally once a day, respectively. The mice in control group were exposed to air, and then injected with an equal volume of normal saline as those in the PPH group every day. All mice were treated for 14 days. Morphological examination of heart and lung tissues was performed using hematoxylin-eosin staining. The expression levels of 11β-HSD2 mRNA and 11β-HSD2 protein in lung tissues were measured by qRT-PCR and Western blot respectively. Brain natriuretic peptide (BNP) and cortisol levels in lung tissues were determined using ELISA.@*RESULTS@#Compared with the control group, the PPH group had significantly increased pulmonary artery wall thickness (WT%), ratio of right to left ventricular thickness (RV/LV), alveolar mean linear intercept, and BNP concentration and a significantly reduced radial alveolar count (P<0.05); compared with the PPH group, the agonist group showed significant increases in WT% and BNP concentration, while the inhibitor group showed significant reductions in the two indicators (P<0.05). Compared with the control group, the PPH group showed significant reductions in the expression levels of 11β-HSD2 mRNA and 11β-HSD2 protein, but a significant increase in cortisol concentration (P<0.05); compared with the PPH group, the agonist group had significantly lower expression levels of 11β-HSD2 mRNA and 11β-HSD2 protein, but a significant higher cortisol concentration, while the inhibitor group showed opposite changes in these indicators (P<0.05).@*CONCLUSIONS@#CaSR may control the development and progression of PPH in newborn mice by regulating the expression of 11β-HSD2 and cortisol concentration.

Effect of calcium-sensitive receptors on endothelial nitric oxide synthase and nitric oxide in neonatal mice with persistent pulmonary hypertension / 中国当代儿科杂志

OBJECTIVE@#To study the effect of calcium-sensitive receptors (CaSR) on the expression of endothelial nitric oxide synthase (eNOS) and the concentration of nitric oxide (NO) in a neonatal mouse model of persistent pulmonary hypertension (PPH).@*METHODS@#Eighty neonatal C57BL/6 mice were randomly divided into control, PPH, agonist and antagonist groups. The control group was exposed to air, and the other three groups were exposed to 12% oxygen. The agonist and antagonist groups were intraperitoneally injected with a CaSR agonist (GdCl 16 mg/kg) and a CaSR antagonist (NPS2390, 1 mg/kg), respectively, while the PPH and control groups were intraperitoneally injected with normal saline instead. All mice were treated for 14 days. Alveolar development and pulmonary vessels were assessed by hematoxylin-eosin staining. The protein and mRNA expression of eNOS and its localization in lung tissues were determined by Western blot, qRT-PCR and immunohistochemistry. The levels of brain natriuretic peptide (BNP) and NO in lung homogenate were determined using ELISA.@*RESULTS@#Compared with the control group, the PPH and agonist groups showed significant increases in alveolar mean linear intercept, the percent wall thickness of pulmonary arterioles, right to left ventricular wall thickness ratio (RV/LV) and BNP concentration, but a significant reduction in radial alveolar count (P<0.05). The antagonist group had significant improvements in all the above indices except RV/LV compared with the PPH and agonist groups (P<0.05). Compared with those in the control group, the protein and mRNA expression of eNOS and NO concentration were significantly increased in the PPH group and increased more significantly in the agonist group, but were significantly reduced in the antagonist group (P<0.05).@*CONCLUSIONS@#CaSR plays an important role in the development of PPH in neonatal mice, possibly by increasing eNOS expression and NO concentration.