EFFECT OF SEX STEROIDS ON RENAL FUNCTION

性类固醇对肾功能的影响

• 批准号: 3426207
• 负责人: CARMEN HINOJOSA-LABORDE
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3426207
• 关键词: angiotensin /renin /aldosterone hypertension; angiotensin II; antihypertensive agents; blood volume; chemical stimulation; estrogens; female; gender difference; hormone regulation /control mechanism; kidney circulation; kidney function; laboratory rat; male; male castration; ovariectomy; phenylephrine; sympathetic nervous system; testosterone

It is well known that the prevalence of hypertension is less in premenopausal women than in men of the same age. In addition, women develop less severe levels of hypertension than men. Although the reason for these sex differences is unknown, it has been proposed that estrogen may protect against hypertension, while testosterone may exaggerate the development of hypertension. The overall objective of this proposal is to determine if there are sex differences in renal function in rats genetically predisposed to hypertension. The hypothesis to be tested is that sex hormones alter renal sodium and water handling such that female rats more efficiently excrete sodium and water than male rats, thus delaying and/or attenuating the development of salt-induced hypertension in females. The proposed studies will be conducted in prehypertensive male and female Dahl salt-sensitive (S) and Dahl salt-resistent (R) rats. These animals will be studied in the intact state, after gonadectomy, and after gonadectomy with sex hormone replacement. Specific Aim #1 is to compare the effects of removal and replacement of estrogen and testosterone on glomerular filtration rate and renal blood flow in normotensive Dahl S and R rats during basal conditions and in response to renal nerve stimulation and administration of phenylephrine, guanabenz and angiotensin II. It is expected that the hemodynamic and tubular responses to circulating vasoconstrictors and renal nerve stimulation will be attenuated in females as compared male rats. Specific Aim #2 is to compare the effects of removal and replacement of estrogen and testosterone on pressure natriuresis and diuresis in normotensive Dahl S and R rats. These experiments will determine if male Dahl S rats have an exaggerated blunting of the pressure natriuresis and diuresis curves as compared to females. Specific Aim #3 is to compare the effect of removal and replacement of estrogen and testosterone on the neural control of renal sodium and water excretion in normotensive Dahl S and R rats by examining diuretic, natriuretic and renal sympathetic nerve activity responses to an acute intravenous volume load. It is hypothesized that male Dahl S rats will respond to volume expansion with an attenuated decrease in renal nerve activity and an attenuated sodium and water excretion as compared to female Dahl S rats.

众所周知，高血压的患病率较小 绝经前女性比同龄男人。 另外，女性 与男性相比，高血压的严重程度较低。 虽然原因 因为这些性别差异尚不清楚，所以已经提出了雌激素 可能预防高血压，而睾丸激素可能会夸大 高血压的发展。 该提议的总体目标是 确定大鼠肾功能的性别差异 遗传上易于高血压。 要检验的假设是 性激素改变肾脏钠和水的处理，使女性 大鼠比雄性大鼠更有效地排泄钠和水，因此 延迟和/或衰减盐引起的高血压的发展 在女性中。 拟议的研究将在高血压前进行 雄性和雌性达尔盐敏感（S）和耐盐（R）大鼠。 这些动物将在完整的状态，性腺切除术后进行，并 性激素替代后性激素切除术后。 具体目标＃1是 比较去除和替代雌激素和 睾丸激素的肾小球滤过率和肾血流 在基础条件下，响应于 肾肾上腺素，鸟根的肾神经刺激和给药 和血管紧张素II。 预计血流动力学和管状 对循环血管收缩和肾神经刺激的反应 与雄性大鼠相比，女性会减弱。 具体目标＃2是 比较雌激素的去除和替代的影响 睾丸激素在正常性dahl s的压力上和利尿 和r老鼠。 这些实验将确定雄性达尔的大鼠是否具有 夸张的压力纳特里列赛和利尿曲线的钝化为 与女性相比。 特定目的＃3是比较去除的效果 并在神经控制上替代雌激素和睾丸激素 正常的Dahl S和R RATS中的肾脏钠和水排泄 检查利尿剂，亚钠和肾交感神经活动 对急性静脉内体积负荷的反应。 假设 雄性达尔（Dahl）的大鼠会因衰减而响应体积的膨胀 减少肾神经活性以及衰减的钠和水 与雌性达尔的大鼠相比排泄。