Gonadotropins in a female model of age-induced hypertension

促性腺激素在女性老年高血压模型中的作用

• 批准号: 8322633
• 负责人: Kathryn L Sandberg
• 金额: $ 15.73万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8322633
• 关键词: Address; Adipose tissue; Adverse effects; Age; Aging; Animal Model; Attenuated; Automobile Driving; Awareness; Basic Science; Biological; Blood Pressure; Blood Vessels; Body Weight; Dahl Hypertensive Rats; Dependency; Disease; Drops; Estradiol; Experimental Models; Feedback; Female; Figs - dietary; Follicle Stimulating Hormone; Functional disorder; Gene Expression; Genes; Genomics; Gonadal Hormones; Gonadal structure; Gonadotropin Hormone Releasing Hormone; Gonadotropins; Health; Hormones; Hypertension; Hypothalamic Hormones; Hypothalamic structure; Insulin; Kidney; Kidney Diseases; Lead; Life; Liver; Longevity; Luteinizing Hormone; Menopause; Modeling; Obesity; Ovarian; Ovarian Follicle; Ovarian hormone; Ovariectomy; Oxidative Stress; Pituitary Gland; Pituitary Hormones; Play; Postmenopause; Premenopause; Prevalence; Progesterone; Publishing; Rattus; Renal Tissue; Renin-Angiotensin System; Reporting; Research; Risk; Rodent Model; Role; Sex Chromosomes; Signal Transduction; Sodium-Restricted Diet; Surveys; Testing; Therapeutic; Tissues; Vascular Diseases; Vasoconstrictor Agents; Weight maintenance regimen; Woman; Women' s Health; age effect; aged; arm; blood pressure regulation; clinically significant; design; dosage; drug efficacy; experience; hormone deficiency; hormone regulation; hypothalamic pituitary ovarian axis; improved; insight; kidney vascular structure; male; men; neglect; normal aging; novel therapeutics; nutrition; prevent; response; salt sensitive; sex

DESCRIPTION (provided by applicant): This project addresses the PA-10-015 by proposing to investigate the role and mechanisms of follicle stimulating hormone (FSH) and leutinizing hormone (LH) in the age-induced increase in blood pressure (BP) and body weight (BW) observed in the female Dahl salt-sensitive (DS) rat. We have previously shown that ovariectomy accelerates the age-induced increase in BP and BW in this model and that 172-estradiol (E2) prevents these effects. Aging and ovariectomy, however, also result in a marked rise in FSH and LH. Though some studies implicate these pituitary hormones in BP regulation, their mechanisms of action are poorly understood. These proposed studies will provide key insight into this experimental model of female aging and postmenopausal hypertension. Aim 1 will determine if preventing the rise in FSH & LH that occurs as a result of ovarian hormone deficiency during normal aging from 4 months old (mo) to 12 mo in the female DS rat will attenuate the age-associated increase in BP, BW, insulin insensitivity, endothelial dysfunction, renal oxidative stress and activation of the vasoconstrictor arm of the renin angiotensin system (RAS) in vascular, renal and adipose tissues. We will also investigate the E2 and progesterone (P4) dependency of these pituitary hormone effects. Aim 2 will serve as the corollary to Aim 1 and will determine if increasing FSH & LH in young (3-4 mo) female DS rats will result in an increase in BP, BW, insulin insensitivity, endothelial dysfunction, renal oxidative stress and activation of the vasoconstrictor arm of the RAS in vascular, renal and adipose tissues. The clinical significance of this research is the insight it will provide into the mechanisms underlying the marked rise in the prevalence of hypertension in women as they age and after their transition into menopause.

描述（由申请人提供）：本项目针对PA-10-015，提出研究促卵泡激素（FSH）和亮氨酸生成素（LH）在雌性达尔盐敏感（DS）大鼠中观察到的年龄诱导的血压（BP）和体重（BW）升高中的作用和机制。我们之前的研究表明，在这个模型中，卵巢切除术加速了年龄引起的血压和体重的增加，而172-雌二醇（E2）可以防止这些影响。然而，衰老和卵巢切除术也会导致FSH和LH显著上升。虽然一些研究暗示这些垂体激素参与血压调节，但它们的作用机制尚不清楚。这些建议的研究将为女性衰老和绝经后高血压的实验模型提供关键的见解。目的1将确定在雌性DS大鼠从4个月大到12个月大的正常衰老过程中，防止卵巢激素缺乏导致的FSH和LH升高是否会减弱与年龄相关的血压、体重、胰岛素不敏感、内皮功能障碍、肾脏氧化应激和血管、肾脏和脂肪组织中肾素血管紧张素系统（RAS）血管收缩肢的激活。我们还将研究E2和孕酮（P4）对这些垂体激素作用的依赖性。Aim 2将作为Aim 1的必然结果，并将确定年轻（3-4个月）雌性DS大鼠FSH和LH的增加是否会导致血压、体重、胰岛素不敏感、内皮功能障碍、肾脏氧化应激和血管、肾脏和脂肪组织中RAS血管收缩臂的激活。这项研究的临床意义在于，它将为女性随着年龄增长和绝经后高血压患病率显著上升的机制提供洞见。