SPONTANEOUS HYPERTENSION: EFFECTS OF EARLY ENVIRONMENT

本提案中描述的实验将评估 交感神经系统发育的早期母体环境 高反应性和血压升高， 高血压（SHR）大鼠，人类原发性高血压动物模型。 我们的实验方法将涉及改变早期母体 SHR和Wistar-Kyoto（WKY）血压正常的窝仔环境， 互惠交叉培养和检查这种治疗的影响， 交感-肾上腺髓质活动的发展和 大鼠，而不受干扰，并在急性暴露于应激刺激。 具体而言，SHR和WKY窝仔将在以下3种条件之一下饲养： (a)（B）由自然母亲抚养的; 由同一品种的养母养育该窝仔;或（c） 交叉寄养--由另一方的养母抚养幼崽 株 通过额外的SHR和WKY窝对照组，我们将 确定母体环境对交感神经系统的影响 活动和高血压是由母体中的应变差异介导的。 行为或通过牛奶传播的高血压原。 评估 母体环境对胎儿发育的影响 交感-肾上腺髓质系统，6个品系处理组的大鼠 (ages 2、4、8、12、16或20天）将注射盐水或胰岛素， 三个小时后被杀。 鸟苷酸脱羧酶的诱导 心脏和肾上腺髓质的肾上腺素消耗将有助于 作为对胰岛素诱导的交感神经刺激的组织反应的标志物。 此外，我们将测试6、12或18周龄的SHR和WKY雄性大鼠 以确定母体环境可能对 行为和生理反应。 对于每个年龄段的大鼠，我们将 测量旷场行为和心率的基础值，平均血液 血压和血浆去甲肾上腺素和肾上腺素水平以及 上述参数中的每一个在急性接触间歇性 脚震 这项研究的结果将提供重要的信息 关于断奶前母体环境对婴儿 交感神经-肾上腺髓质系统的发育 高血压和正常血压大鼠。 此外，我们的研究将澄清， 断奶后SHR大鼠交感神经高反应性的意义 在急性应激期间，这是高血压发展的一个危险因素。

The experiments described in this proposal will evaluate the role of the early maternal environment in the development of sympathetic nervous system hyperreactivity and elevated blood pressure in the spontaneously hypertensive (SHR) rat, an animal model of human essential hypertension. Our experimental approach will involve altering the early maternal environment of SHR and Wistar-Kyoto (WKY) normotensive litters by reciprocal cross-fostering and examining the effects of this treatment on the development of sympathetic-adrenal medullary activity and behavior of rats while undisturbed and during acute exposure to stressful stimulation. Specifically, SHR and WKY litters will be reared under 1 of 3 conditions: (a) control- rearing of the litter by the natural mother; (b) in-fostered- rearing of the litter by a foster mother of the same strain; or (c) cross-fostered- rearing of the litter by a foster mother of the opposite strain. With additional control groups of SHR and WKY litters, we will determine if the effects of the maternal environment on sympathetic activity and hypertension are mediated by strain differences in maternal behavior or by a hypertensinogen transmitted through the milk. To assess the effects of the maternal environment on the development of the sympathetic-adrenal medullary system, rats of the 6 strain-treatment groups (ages 2,4,8,12,16, or 20 days) will be injected with saline or insulin and sarcrificed 3 hours later. The induction of ornithine decarboxylase in heart and the depletion of epinephrine from the adrenal medulla will serve as markers of tissue responses to insulin-induced sympathetic stimulation. In addition, we will test SHR and WKY male rats at 6, 12 or 18 weeks of age to determine possible long term effects of the maternal environment on behavioral and physiological responses. For rats at each age, we will measure open field behavior and basal values of heart rate, mean blood pressure and plasma levels of nerepinephrine and epinephrine and changes in each of the above parameters following acute exposure to intermittent footshock. The results of this research will provide important information regarding the impact of the preweaning maternal environment on the development of the sympathetic-adrenal medullary system in genetically hypertensive and normotensive rats. Further, our studies will clarify in post-weaned SHR rats the significance of sympathetic hyperresponsiveness during acute stress as a risk factor for the development of hypertension.