DiBona Gerald F, Jones Susan Y
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Auton Neurosci. 2002 Jun 28;98(1-2):17-9. doi: 10.1016/s1566-0702(02)00023-1.
The role of central angiotensinergic pathways in the cardiovascular regulation has been examined using the microinjection of angiotensin peptides and angiotensin receptor antagonists. However, in such studies, neither the overall nor the local level of activity of the renin-angiotensin system is generally known. Herein, physiological changes in the endogenous level of activity of the renin-angiotensin system were produced by alterations in the dietary sodium intake. Microinjection of the angiotensin II AT1 receptor antagonists losartan or candesartan into the rostral ventrolateral medulla produced the bradycardic, depressor and renal sympathoinhibitory responses which were greater in low sodium diet rats with stimulated activity of the renin-angiotensin system than in high sodium diet rats with suppressed activity of the renin-angiotensin system activity. The renal sympathoexcitatory responses to activation of the paraventricular nucleus by microinjection of bicuculline, known to be dependent on the excitatory synaptic inputs to the rostral ventrolateral medulla mediated by AT1 receptors, were greater in low sodium diet rats than in high sodium rats. These observations support the view that physiologically regulated angiotensin peptides of the brain origin exert a local paracrine or autocrine action on sites that influence the renal sympathetic nerve activity.
利用血管紧张素肽和血管紧张素受体拮抗剂的微量注射,已对中枢血管紧张素能通路在心血管调节中的作用进行了研究。然而,在这类研究中,肾素-血管紧张素系统的整体活性水平和局部活性水平通常都不清楚。在此,通过改变饮食中的钠摄入量,使肾素-血管紧张素系统的内源性活性水平发生生理变化。将血管紧张素II AT1受体拮抗剂氯沙坦或坎地沙坦微量注射到延髓头端腹外侧,会产生心动过缓、降压和肾交感神经抑制反应,在肾素-血管紧张素系统活性受刺激的低钠饮食大鼠中,这些反应比在肾素-血管紧张素系统活性受抑制的高钠饮食大鼠中更明显。通过微量注射荷包牡丹碱激活室旁核所产生的肾交感神经兴奋反应,已知该反应依赖于由AT1受体介导的对延髓头端腹外侧的兴奋性突触输入,在低钠饮食大鼠中比在高钠大鼠中更明显。这些观察结果支持这样一种观点,即源自大脑的经生理调节的血管紧张素肽对影响肾交感神经活动的部位发挥局部旁分泌或自分泌作用。