ADRENERGIC DYSFUNCTION IN UREMIA

部分肾切除尿毒症大鼠提供了一个很好的模型， 研究尿毒症对肾上腺素能神经系统的影响。 采用 尿毒症大鼠肠系膜血管制备和γ 1，选择性 放射性配体（125 I）IBE 2254，尿毒症对肾上腺素能效应子的影响 全身血管阻力的组成部分; γ 1，血管受体， 将被评估。 要检验的假设是慢性尿毒症导致 一种神经源性高血压，类似于实验中观察到的高血压。 压力感受器分化模型。 在这样的模型中， 抑制交感神经血管流出，导致交感神经 介导的血管收缩，增加的儿茶酚胺合成和 高血压 具体目标包括： 1)为了确定γ 1血管受体的数量是否减少， 尿毒症大鼠 以内源性增加为特征的生理状态 儿茶酚胺的水平与γ-肾上腺素的下调有关， 1血管受体。 通过测定血浆儿茶酚胺水平，我们将 能够将这些与观察到的受体数量的任何变化相关联。 2)为了确定γ 1血管受体的亲和力是否钝化， 或因尿毒症状态而减少。 在一系列相关的调查也进行了尿毒症大鼠 慢性尿毒症对心肌B密度和亲和力的影响 肾上腺素能受体;和B受体;腺苷酸环化酶偶联，将是 考察

The partially nephrectomized uremic rat provides an excellent model to examine the effect of uremia on the adrenergic nervous system. Employing the uremic rat mesenteric vascular preparation, and the Gamma 1, selective radioligand (125I) IBE2254, the effect of uremia on the adrenergic effector component of systemic vascular resistance; the Gamma 1, vascular receptor, will be assessed. The hypothesis to be tested is chronic uremia results in a neurogenic form of hypertension, similar to that observed in experimental models with baroreceptor differentation. In such models, loss of tonic inhibition of sympathetic vasomotor outflow, results in sympathetically mediated vasoconstriction, increased catecholamine synthesis and hypertension. Specific objectives include: 1) To determine if the number of Gamma 1 vascular receptors is decreased in uremic rats. Physiologic states characterized by increased endogenous levels of catecholamines have been associated with down regulation of Gamma 1 vascular receptors. By determining plasma catecholamine levels, we will be able to correlate these with any changes in receptor number observed. 2) To determine if the affinity of the Gamma 1 vascular receptor is blunted or decreased by the uremic state. In a series of related investigations also performed in the uremic rat model, the effect of chronic uremia on density and affinity of myocardial B adrenergic receptors; and B receptor; adenyl cyclase coupling, will be examined.