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Androgens raise venous and arterial adrenergic tone.

雄激素提高静脉和动脉肾上腺素能张力。

基本信息

批准号：
7864223
负责人：
DOUGLAS S MARTIN
金额：
$ 31.2万
依托单位：
UNIVERSITY OF SOUTH DAKOTA
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-09-15 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7864223
关键词：
Address Adrenergic Agents Adrenergic Receptor Adverse effects Affect Age Androgen Receptor Androgens Angiotensins Animal Model Animals Antihypertensive Agents Arteries Atherosclerosis Attention Autonomic nervous system Back Biochemical Blood Circulation Blood Pressure Blood Vessels Brain Cardiac Output Cardiovascular Diseases Cardiovascular system Castration Chronic Data Development Dose Down-Regulation Drops Echocardiography Essential Hypertension Estrogens Feedback Gene Expression Genotype Gonadal Steroid Hormones Heart Rate Heart failure Homeostasis Human Hydralazine Hypertension Hypotension Hypothalamic structure In Vitro Inbred SHR Rats Inbred WKY Rats Indium Intervention Investigation Kidney Failure Laboratories Lead Literature Male Castration Measures Mediating Mesentery Modeling Monitor Myocardial Infarction N-Type Calcium Channels Nerve Neuraxis Norepinephrine Orthostatic Hypotension Pathway interactions Patients Pattern Peripheral Peripheral Resistance Pharmaceutical Preparations Play Population Preparation Process Protein Kinase C Proteins Public Health Rattus Receptor Activation Regulation Regulatory Element Research Reverse Transcriptase Polymerase Chain Reaction Rho-associated kinase Risk Factors Role Signal Transduction Site Smooth Muscle Staging Stanolone Stroke Sympathetic Nervous System System Testing Testosterone Time Trees Vascular Smooth Muscle Vascular resistance Vasodilation Veins Venous Venous Pressure level Western Blotting Work adrenergic blood pressure regulation cationic antimicrobial protein CAP 37 cellular targeting cohort design direct application feeding hemodynamics in vivo male neuromechanism neurotransmission non-genomic normotensive operation paraventricular nucleus pressure presynaptic research study response rho subcutaneous vascular bed

项目摘要

The development of hypertension is sexually dimorphic. Blood pressure rises more quickly and to a greater extent in males. While considerable research attention has been directed toward the arterial circulation, there has been relatively little investigation of venous changes in hypertension. Our previous work indicated that venous tone was elevated by neural mechanisms in the developmental stages of hypertension in the spontaneously hypertensive rat, an animal model of that resembles essential hypertension in humans. Recent data suggest that veins and arteries are affected differently by hypertension. Thus, this project will test the general hypothesis that androgens amplify adrenergic tone of the arterial and venous vascular compartments via different mechanisms. Specific aim I will address the possibility that this effect occurs at the level of vascular smooth muscle. Specific aim II will assess the role of changes in norepinephrine release mechanisms. Specific aim III will investigate the effects of androgens on CNS mechanisms controlling sympathetic nervous system outflow from the hypothalamus. Functional studies will be conducted in vivo and in isolated perfused vascular beds. Androgen induced changes in protein and gene expression will be assessed with Western blot and real time RT-PCR approaches. Collectively we expect these studies to show that androgens amplify adrenergic tone in veins and arteries but that the underlying mechanisms are different in these two vascular compartments. These data will expand our understanding of sex steroid modulation of vascular function and of hypertension development. Hypertension is a significant public health problem that is a risk factor for many other cardiovascular diseases. In addition, in patients hypertension is poorly controlled. Moreover, postural hypotension is common adverse effect of antihypertensive therapy, implying dysregulation of venous function. A better understanding the factors that control arterial and venous tone in hypertension may lead to design antihypertensive drugs with fewer adverse effects

高血压的发展是性二态的。血压上升得更快，更高在男性中的范围。虽然相当多的研究注意力都指向动脉循环，但有目前对高血压静脉病变的研究相对较少。我们之前的工作表明，在高血压的发展阶段，神经机制使静脉张力升高自发性高血压大鼠，一种类似于人类高血压的动物模型。近期数据表明，高血压对静脉和动脉的影响是不同的。因此，该项目将测试雄激素增强动脉和静脉血管间室肾上腺素能张力的一般假设通过不同的机制。具体目标我将讨论这种影响发生在血管平滑肌。SPARTIC AIM II将评估去甲肾上腺素释放变化的作用机制。特殊目的III将研究雄激素在中枢神经系统控制机制中的作用交感神经系统从下丘脑流出。功能研究将在体内进行，并在隔离的灌流血管床中。雄激素诱导的蛋白质和基因表达的变化将是用Western印迹和实时RT-PCR方法进行检测。总而言之，我们希望这些研究表明雄激素能增强静脉和动脉的肾上腺素能张力，但潜在的机制是不同的在这两个血管隔间里。这些数据将扩大我们对性激素调节的理解。血管功能和高血压的发生发展。高血压是一个重大的公共卫生问题，是许多其他心血管疾病的危险因素。此外，在患者中，高血压控制得很差。此外，体位性低血压是降压治疗的常见不良反应，意味着调节失调。静脉功能。更好地了解高血压患者动静脉张力的控制因素可能导致设计副作用较少的降压药

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Vascular ECE-1 mRNA expression decreases in response to estrogens.

血管 ECE-1 mRNA 表达因雌激素而降低。

DOI：
10.1016/j.lfs.2003.05.001
发表时间：
2003
期刊：
Life sciences
影响因子：
6.1
作者：
Rodrigo,ManojC;Martin,DouglasS;Eyster,KathleenM
通讯作者：
Eyster,KathleenM

Dietary soy exerts an antihypertensive effect in spontaneously hypertensive female rats.

膳食大豆对自发性高血压雌性大鼠具有抗高血压作用。

DOI：
10.1152/ajpregu.2001.281.2.r553
发表时间：
2001
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
0
作者：
Martin,DS;Breitkopf,NP;Eyster,KM;Williams,JL
通讯作者：
Williams,JL

Estrogen decreases biglycan mRNA expression in resistance blood vessels.

雌激素降低阻力血管中双糖链蛋白聚糖 mRNA 的表达。

DOI：
10.1152/ajpregu.00540.2002
发表时间：
2003
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
0
作者：
Rodrigo,ManojC;Martin,DouglasS;Eyster,KathleenM
通讯作者：
Eyster,KathleenM

Castration reduces blood pressure and autonomic venous tone in male spontaneously hypertensive rats.

去势可降低雄性自发性高血压大鼠的血压和自主静脉张力。