LOSARTAN IMPROVES VENTILATION IN DYSTROPHIC HAMSTERS

氯沙坦改善营养不良仓鼠的通气

• 批准号: 7627584
• 负责人: EVELYN Heymann SCHLENKER
• 金额: $ 1.03万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627584
• 关键词: Affect; Angiotensin II; Animal Model; Cardiac; Cardiovascular Physiology; Chronic; Computer Retrieval of Information on Scientific Projects Database; Dopamine; Dopamine Receptor; Endocrine; Environmental air flow; Exhibits; Fibrosis; Functional disorder; Funding; Grant; Hamsters; Heart; Hypoxemia; Institution; Limb-Girdle Muscular Dystrophies; Losartan; Neuraxis; Personal Satisfaction; Production; Purpose; Receptor, Angiotensin, Type 1; Research; Research Personnel; Resources; Skeletal Muscle; Source; Structure; System; Testing; Tyrosine 3-Monooxygenase; United States National Institutes of Health; dopaminergic neuron; improved; receptor; receptor function

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The BIO 14.6 hamster, an animal model of limb-girdle muscular dystrophy demonstrates compromised ventilation resulting in hypoxemia that may exacerbate cardiac and skeletal muscle dysfunction. This animal model also exhibits levels of angiotensin II and angiotensin AT1 receptors. Not only is this system active as a classic endocrine, it is also found in the central nervous system where it modulates CNS function including dopaminergic neuron integrity, tyrosine hydroxylase expression, dopaminergic release and dopaminergic receptor function. The purpose of this proposal is to test the hypothesis that chronic losartan (an AT1 receptor antagonist) administration will improve ventilation in dystrophic hamsters by 1. improving diaphragmatic structure and function (as suggested by the recent study by Cohn and colleagues) and 2. decreasing TH expression, dopamine production, and normalizing dopamine receptor function. Another factor that may affect ventilation is that losartan augments cardiovascular function in dystrophic hamsters. Although this is well documented, we will also determine if structural changes in the dystrophic heart such as increased fibrosis are also improved by losartan function.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 BIO 14.6 仓鼠是肢带型肌营养不良症的动物模型，其通气功能受损，导致低氧血症，可能会加剧心脏和骨骼肌功能障碍。该动物模型还表现出血管紧张素 II 和血管紧张素 AT1 受体的水平。该系统不仅作为经典内分泌系统具有活性，而且还存在于中枢神经系统中，调节中枢神经系统功能，包括多巴胺能神经元完整性、酪氨酸羟化酶表达、多巴胺能释放和多巴胺能受体功能。本提案的目的是检验以下假设：长期服用氯沙坦（一种 AT1 受体拮抗剂）将通过以下方式改善营养不良仓鼠的通气：1. 改善膈肌结构和功能（正如 Cohn 及其同事最近的研究所表明的那样）；2. 减少 TH 表达、多巴胺产生和使多巴胺受体功能正常化。另一个可能影响通气的因素是氯沙坦增强营养不良仓鼠的心血管功能。尽管这一点已有充分记录，但我们还将确定氯沙坦功能是否也能改善营养不良性心脏的结构变化（例如纤维化增加）。