VASOPRESSIN IN PATHOGENESIS OF DOCA/SALT HYPERTENSION

越来越多的证据表明，血管加压素（VP）可能发挥作用，在 DOCA/盐性高血压的发展。 最重要的发现是 VP缺乏的Brattleboro大鼠（DI大鼠）不能发展为高血压， 用DOCA/盐处理，但当用VP代替时，则如此。 知之甚少 VP在高血压中的作用机制。 本研究计划建议确定作用机制 DOCA/盐性高血压的VP。 VP可以作为直接 血管收缩剂/升压剂。 我们将研究直接 VP的血管收缩/升压作用在光伴随的活动， 交感神经系统和压力感受器反射。 血管 将在未麻醉的DOCA/盐处理的 用慢性导管和脉冲多普勒血流探头对大鼠进行检测， 交感神经阻滞前后高血压的各个阶段 神经系统或窦主动脉传入阻滞。 VP可以作为 抗利尿剂。 这将通过评估体液的变化来测试 容量、肾功能以及水和电解质代谢 高血压的发展过程。 VP可间接调节 血管平滑肌对其他血管收缩剂反应性 特别是儿茶酚胺。 这将通过评估血管 在隔离的灌注血管床中的反应性。 最后，VP可以调节 控制压力感受器反射的中枢神经靶区的功能， 交感神经流出 这将由以下人员进行测试： 1)确定VP与蓝斑、核的相互作用 孤束和下丘脑后部， 推拉灌注和脑打孔技术2）确定效果 室旁核和视上核的刺激 压力反射功能 3)确定VP与中心的相互作用 儿茶酚胺能神经元 这些实验的结果应该提供 VP在正常心血管疾病中作用的基本信息 调节以及高血压的发病机制。

Increasing evidence suggests that vasopressin (VP) may play a role in the development of DOCA/salt hypertension. Of great importance is the finding that VP-deficient Brattleboro rats (DI rats) fail to develop hypertension with DOCA/salt treatment but do so when replaced with VP. Little is known of the mechanism of action of VP in hypertension. The present research plan proposes to identify the mechanism(s) of action of VP in DOCA/salt hypertension. VP may function as a direct vasoconstrictor/pressor agent. We will study the direct vasoconstrictor/pressor effect of VP in light concomitent activity of the sympathetic nervous system and the baroreceptor reflex. Vascular reactivity to VP will be assessed in the unanesthetized DOCA/salt treated rats instrumented with chronic catheters and pulsed-Doppler flow probes at various stages of hypertension before and after blockade of the sympathetic nervous system or sinoaortic deafferentation. VP may act as an antidiuretic agent. This will be tested by assessing changes in body fluid volumes, renal function and water and electrolyte metabolism over the course of development of hypertension. VP may act indirectly to modulate the responsiveness of vascular smooth muscle to other vasoconstrictors particularly catecholamines. This will be tested by assessing vascular reactivity in isolated, perfused vascular beds. Finally, VP may modulate the function of central neural target areas controlling the baroreflex and sympathetic outflow. This will be tested by 1) determining the interaction of VP with the locus coeruleus, nucleus tractus solitarii, and posterior hypothalamus using microinjection, push-pull perfusion and brain punch techniques 2) determining the effects of stimulation of the paraventricular and supraoptic nuclei on the baroreflex function. 3) determining the interaction of VP with central catecholaminergic neurons. The results of these experiments should provide fundamental information on the role of VP in normal cardiovascular regulation as well as in the pathogenesis of hypertension.