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NITRIC OXIDE CONTROL OF UTERINE CONTRACTILITY

一氧化氮控制子宫收缩

基本信息

批准号：
2403297
负责人：
CHANDRASEKHAR YALLAMPALLI
金额：
$ 14.4万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-08-01 至 1999-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2403297
关键词：
amine oxidoreductase arginine birth cyclic GMP enzyme activity hormone regulation /control mechanism human subject immunocytochemistry laboratory rat muscle contraction nitric oxide northern blottings nucleic acid probes phosphodiesterases polymerase chain reaction pregnancy protein isoforms uterus

项目摘要

Uterine quiescence during pregnancy, until term, is required for successful completion of gestation by providing a tranquil environment for the growing fetus. Failure to maintain uterine relaxation until term results in preterm delivery, which is the leading cause of infant mortality and morbidity. Recent evidence suggests that nitric oxide (NO) is a potent mediator of smooth muscle relaxation. We initiated studies to examine if an L-arginine-NO-cGMP-relaxation system is present in the rat uterus and if it inhibits contractility. Our preliminary studies provide strong evidence for the presence of a NO-relaxation pathway in the rat uterus and suggest that this system might play a role in maintaining uterine quiescence during pregnancy. To extend these studies we propose to test the following hypotheses: a. A L-arginine NO-cGMP-pathway is present in the uterus and that it specifically inhibits uterine contractility. b. The NO-cGMP-relaxation pathway is upregulated during pregnancy. c. The generation of NO-cGMP and relaxation effects of NO-cGMP are hormonally regulated. The specific aims of this study are: 1. To further establish the existence of a NO-cGMP-relaxation system in the uterus and determine if NO is produced in the uterus. For this we will use various agents to modulate the pathway and measure uterine contractility in vitro. 2. To localize nitric oxide synthase (NOS) activity in the uterine tissues and to ascertain which isoform(s) of NOS are present in this tissue. 3. To investigate whether the NO-cGMP-relaxation system is upregulated during pregnancy and if it is hormone regulated. 4. To examine the mechanisms involved in the NO-cGMP regulation of uterine contractility. 5. To ascertain whether manipulation of the NO-cGMP cascade during pregnancy will affect the pregnancy outcome. 6. To investigate the existence of NO-cGMP system in the human uterus and determine if the uterus reacts to this system differently in pregnant delivering, nondelivering and nonpregnant women. To accomplish these studies, we will use pharmacological studies of in vitro contractility measurement, biochemical assays for NO and cGMP production, arginine to citrulline conversion, histochemical localization and determine the isoform(s) of the NOS in the uterus. These studies will provide important information on the mechanisms through which uterine contractility is regulated during gestation and initiation of labor. Knowledge from these studies may provide the basis for designing appropriate therapeutic strategies to reduce preterm labor.

在怀孕期间，子宫静止，直到足月，是必需的