Effect of calcium-sensitive receptors on endothelial nitric oxide synthase and nitric oxide in neonatal mice with persistent pulmonary hypertension.
- Author:
Xiang LI
1
;
Bing-Xia WU
;
He LI
;
Meng-Meng WANG
;
Ke-Tao MA
;
Qiang GU
Author Information
1. Department of Pediatrics, First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang 832000, China. guqiang106@sina.com.
- Publication Type:Journal Article
- MeSH:
Animals;
Animals, Newborn;
Calcium;
Hypertension, Pulmonary;
Hypoxia;
Mice;
Mice, Inbred C57BL;
Nitric Oxide;
Nitric Oxide Synthase Type III;
Receptors, Calcium-Sensing
- From:
Chinese Journal of Contemporary Pediatrics
2019;21(2):189-194
- CountryChina
- Language:Chinese
-
Abstract:
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.
