VASOPRESSIN IN PATHOGENESIS OF DOCA/SALT HYPERTENSION

越来越多的证据表明，加压素(VP)可能在 DOCA/盐性高血压的进展。非常重要的是这一发现 缺乏VP的Brattleboro大鼠(DI大鼠)不会发生高血压 使用DOCA/盐治疗，但在替换为VP时这样做。鲜为人知 VP在高血压中的作用机制。 本研究计划提出要明确作用机制(S) DOCA/盐性高血压的VP。VP可以起到直接的作用 血管收缩/升压剂。我们将研究直接 VP的血管收缩/升压效应在大鼠脑内的轻度伴随活动中的作用 交感神经系统和压力感受器反射。血管 对VP的反应性将在未麻醉的DOCA/盐处理中进行评估 使用慢性导管和脉冲多普勒血流探头的大鼠 交感神经阻断前后高血压的不同阶段 神经系统或窦主动脉去传入。副总裁可担任 抗利尿剂。这将通过评估体液的变化来测试 血容量、肾功能、水和电解质代谢 高血压的发展历程。VP可能间接起到调节作用 血管平滑肌对其他血管收缩药的反应性 尤其是儿茶酚胺。这将通过评估血管 在隔离的、灌流的血管床中的反应性。最后，VP可能会调整 中枢神经靶区对压力感受性反射的调控作用 感同身受的流出。这将通过以下方式进行测试 1)测定VP与蓝斑、蓝核的相互作用 孤束和下丘脑后部微量注射， 推拉灌流和脑打孔技术2)确定效果 刺激室旁核和视上核对视上核的影响 压力反射功能。3)确定VP与中枢的相互作用 儿茶酚胺能神经元。这些实验的结果应该提供 VP在正常心血管系统中作用的基础信息 调节作用以及在高血压发病机制中的作用。

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.