ABSTRACT
In this study, we used a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) to investigate the role and mechanism of angiotensin (Ang)-(1-7) in regulating pulmonary artery diastolic function. Three weeks after subcutaneous injection of MCT or normal saline, the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) of rats were detected using a right heart catheter. Vascular endothelium-dependent relaxation was evaluated by acetylcholine (ACh)-induced vasodilation. The relaxation function of vascular smooth muscle was evaluated by sodium nitroprusside (SNP)-induced vasodilation. Human pulmonary artery endothelial cells (HPAECs) were incubated with Ang-(1-7) to measure nitric oxide (NO) release levels. The results showed that compared with control rats, RVSP and RVHI were significantly increased in the MCT-PAH rats, and both ACh or SNP-induced vasodilation were worsened. Incubation of pulmonary artery of MCT-PAH rats with Ang-(1-7) (1 × 10-9-1 × 10-4 mol/L) caused significant vaso-relaxation. Pre-incubation of Ang-(1-7) in the pulmonary artery of MCT-PAH rats significantly improved ACh-induced endothelium-dependent relaxation, but had no significant effect on SNP-induced endothelium-independent relaxation. In addition, Ang-(1-7) treatment significantly increased NO levels in HPAECs. The Mas receptor antagonist A-779 inhibited the effects of Ang-(1-7) on endothelium-dependent relaxation and NO release from endothelial cells. The above results demonstrate that Ang-(1-7) promotes the release of NO from endothelial cells by activating Mas receptor, thereby improving the endothelium-dependent relaxation function of PAH pulmonary arteries.
Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Rats , Humans , Animals , Vasodilation , Monocrotaline/toxicity , Rats, Sprague-Dawley , Hypertension, Pulmonary/chemically induced , Endothelial Cells , Pulmonary Artery , Endothelium , Acetylcholine/pharmacology , Nitroprusside/pharmacologyABSTRACT
The objective of this study was to analyze the effects of single and combined genotypes of MC4R and POU1F1 genes in Chinese well-known indigenous chicken (Langshan chicken) population. Genetic variants within MC4R gene and POU1F1 gene were screened through PCR-SSCP and DNA sequencing methods. A C/T mutation at nt 944 in MC4R gene (NC_006089.2:g. 944C>T) and a G/A mutation at nt 3109 in POU1F1 gene (NC_006088.2:g. 3109 G>A) were identified. Associations between the mutations of the two genes with two production traits were analyzed. The results showed that, at MC4R locus, individuals with BB and AB genotypes had highly significantly higher body weight at 16 weeks (p < 0.01) than did those with the AA genotype. And, individuals within AA and AB genotypes had significantly higher egg numbers at 300 days (p < 0.05). At POU1F1 locus, individuals with CD genotype had higher body weight at 16 weeks and egg numbers at 300 days (p < 0.05). Furthermore, combined genotypes from these two loci were found to be associated with egg numbers at 300 days (p < 0.05). The individuals within combined genotype AB/CD had higher egg production. Therefore, variations identified within the MC4R and POU1F1genes are suitable for future use in identifying chickens with the genetic potential of higher body weight and reproductive traits, at least in the population of Langshan chickens.
