MECHANISMS IN THE REGULATION OF UTERINE BLOOD FLOW
(1981)
Abstract :
The objective of the proposed investigation is directed toward elucidating the mechanisms by which estrogens, through other mediators, regulate blood flow through the uterine vascular bed. Prostacyclin (PGI2) appears to play a significant role as a mediator in this process, and we have shown it to be a potent uterine vasodilator. We will study the effects of prostacyclin synthetase inhibition on estrogen-induced uterine blood flow and uterine vascular resistance. In addition, we will measure the uterine production rates of thromboxane B2 and 6-keto-PGF1 alpha in response to estrogen stimulation with and without PGI2 synthetase inhibition. Finally, we will explore the inter-relationship of cycloheximide on adenosine and arachidonic acid-induced increases in uterine blood flow.
| Project Number : | 5R01HD011504-02 |
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| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
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| IRG : | HED |
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| Project Terms : | CARDIOVASCULAR FUNCTION, BLOOD FLOW, EMBRYOLOGY (HUMAN) AND DEVELOPMENT STUDY SECTION, FATTY ACIDS METABOLISM, PROSTAGLANDINS METABOLISM, REPRODUCTIVE SYSTEM FEMALE, UTERUS, reproductive system circulation CARDIOVASCULAR FUNCTION, BLOOD FLOW, REACTIVE HYPEREMIA, ENDOCRINOLOGY, HORMONAL REGULATION AND CONTROL (MECHANISMS), ESTRATRIENE SERIES, ESTROGENS, FATTY ACIDS, ARACHIDONIC ACID, FATTY ACIDS, UNSATURATED, PROSTAGLANDINS, ANTIPROSTAGLANDINAGENTS, FATTY ACIDS, UNSATURATED, PROSTAGLANDINS, PROSTACYCLIN, PURINE NUCLEOSIDES, ADENINE NUCLEOSIDES, ADENOSINE, cardiovascular pharmacology ADRENAL CORTEX HORMONES, ANTIBIOTICS, CYCLOHEXIMIDE, BENZOPYRROLE CARBOXYLIC ACIDS, INDOMETHACIN, CARDIOVASCULAR DISORDERS DIAGNOSIS, BLOOD FLOW MEASUREMENTS, ELECTROMAGNETIC, DOSAGE AND ROUTE, INFUSIONS ARTERIAL, MAMMALS, ARTIODACTYLA, SHEEP |
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MECHANISMS IN THE REGULATION OF UTERINE BLOOD FLOW
(1981)
Abstract :
Estrogens are well known to produce dramatic increases in uterine blood flow. This estrogen-induced response is produced by activation of some mediator(s) rather than a direct effect of the hormone on the vessel wall. Agents such as adenosine, the adenine nucleotides, and the prostaglandins are known to be potent uterine vasodilators, and have been proposed to mediate the estrogen-stimulated response. Recent evidence strongly suggests that prostacyclin, a product of endoperoxide metabolism synthesized in vascular endothelium, is the local regulator of vasodepressor responses in numerous organs and in various species. The fact that prostaglandin synthesis and estrogen-induced uterine blood flow are both inhibited by corticosteroids makes attractive a hypothesis which links prostacyclin synthesis to the estrogen-blood flow response. Utilizing a well-established sheep model, specifically designed for continuous blood flow measurements in the chronic state, we propose to explore the role of the prostaglandins and adenosine in the regulation of uterine blood flow by (1) observing the blood flow responses to intra-arterial infusions of prostacyclin and arachidonic acid, (2) attempting to suppress estrogen and arachidonic acid induced flow increases with inhibitors of prostaglandin synthesis, and (3) elucidating the relationship between adenosine and prostaglandin synthesis. The proposed study should provide basic information relating to the regulation of uterine blood flow and ultimately improve our understanding of perinatal well-being.
| Project Number : | 1R01HD011504-01A1 |
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| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
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| IRG : | HED |
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| Project Terms : | CARDIOVASCULAR FUNCTION, BLOOD FLOW, EMBRYOLOGY (HUMAN) AND DEVELOPMENT STUDY SECTION, FATTY ACIDS METABOLISM, PROSTAGLANDINS METABOLISM, REPRODUCTIVE SYSTEM FEMALE, UTERUS, reproductive system circulation CARDIOVASCULAR FUNCTION, BLOOD FLOW, REACTIVE HYPEREMIA, ENDOCRINOLOGY, HORMONAL REGULATION AND CONTROL (MECHANISMS), ESTRATRIENE SERIES, ESTROGENS, FATTY ACIDS, ARACHIDONIC ACID, FATTY ACIDS, UNSATURATED, PROSTAGLANDINS, ANTIPROSTAGLANDINAGENTS, FATTY ACIDS, UNSATURATED, PROSTAGLANDINS, PROSTACYCLIN, PURINE NUCLEOSIDES, ADENINE NUCLEOSIDES, ADENOSINE, cardiovascular pharmacology ADRENAL CORTEX HORMONES, ANTIBIOTICS, CYCLOHEXIMIDE, BENZOPYRROLE CARBOXYLIC ACIDS, INDOMETHACIN, CARDIOVASCULAR DISORDERS DIAGNOSIS, BLOOD FLOW MEASUREMENTS, ELECTROMAGNETIC, DOSAGE AND ROUTE, INFUSIONS ARTERIAL, MAMMALS, ARTIODACTYLA, SHEEP |
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NICOTINE EFFECT ON MATERNAL FETAL VASCULAR HOMEOSTASIS
(1981)
Abstract :
Smoking during pregnancy has been shown to decrease infant birth weight and to substantially increase both perinatal morbidity and mortality. Among the major components of cigarette smoke, the physiologic aberrations produced by carbon monoxide have been extensively investigated. Less is known about the physiologic effects of nicotine on the pregnant uterus and its contents. Utilizing a well-established sheep model, specifically designed for continuous blood flow measurements and blood sampling, we have been able to delineate the effects of nicotine on uterine blood flow. Following systemic nicotine infusion, uterine blood flow decreases, a response which is mediated by release of catecholamines. We propose to extend these observations by simultaneous measurements of: (1) umbilical blood flow, (2) maternal and fetal plasma nicotine concentrations, (3) fetal acid base status, and (4) fetal plasma catecholamine concentrations. The proposed study should provide information relating to the mechanisms by which nicotine influences uterine and umbilical blood flow, and ultimately improve our understanding of how smoking endangers fetal health.
| Project Number : | 1R01HD014154-01 |
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| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
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| IRG : | HED |
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| Project Terms : | CARDIOVASCULAR FUNCTION, BLOOD FLOW, CARDIOVASCULAR FUNCTION, VASCULAR RESISTANCE, EMBRYOLOGY (HUMAN) AND DEVELOPMENT STUDY SECTION, PREGNANCY, EMBRYO-FETUS, PYRIDINES, NICOTINE, pregnancy circulation BODY FLUID BALANCE, ACID-BASE, CARDIOVASCULAR FUNCTION, BLOOD CIRCULATION DYNAMICS (GENERAL), CARDIOVASCULAR FUNCTION, BLOOD PRESSURE, HEART FUNCTION, HEART RATE, INFORMATION PROCESSING AND CONTROL (BIOLOGICAL), HOMEOSTASIS, PHENYLALKYLAMINES, CATECHOLAMINES, PREGNANCY CIRCULATION, PLACENTAL TRANSFER, PREGNANCY FLUIDS, AMNIOTIC FLUID, PREGNANCY, EMBRYO-FETUS, GESTATIONAL AGE, PREGNANCY, UMBILICAL CORD, PSYCHOLOGY, HABITS, SMOKING, RESPIRATORY GASES CARDIOVASCULAR DISORDERS DIAGNOSIS, BLOOD FLOW MEASUREMENTS, ELECTROMAGNETIC, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, RADIOIMMUNOASSAY, MAMMALS, ARTIODACTYLA, SHEEP, PHYSICAL SEPARATION, CHROMATOGRAPHY, THIN LAYER, RESPIRATORY GAS ANALYZERS |
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