Harding J W, Jensen L L, Hanesworth J M, Roberts K A, Page T A, Wright J W
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, College of Veterinary Medicine, Washington State University, Pullman 99164-6520.
Am J Physiol. 1992 Jan;262(1 Pt 2):F17-23. doi: 10.1152/ajprenal.1992.262.1.F17.
The brain angiotensin (ANG II and III) system is known to play an important role in the central control of cardiovascular function and body water homeostasis. A number of components of the angiotensin system including active peptides, precursors, synthetic enzymes, and receptors have been localized to specific brain nuclei including the paraventricular nucleus (PVN) of the hypothalamus. We and others have hypothesized that the PVN is a major integrative hub of the central angiotensin system receiving angiotensinergic input from central detectors (circumventricular organs) and sending efferents to higher brain and spinal cord centers. Implicit in this idea is that angiotensins, like all neurotransmitters, should be releasable with appropriate chemical and physiological stimuli. Therefore we examined the ability of water deprivation or direct infusion of either 65 mM K+ or 80 microM veratridine to stimulate the release of angiotensins from the PVN of the rat. Using push-pull cannulas to perfuse the PVN and radioimmunoassay (RIA) to analyze the superfusate for immunoreactive angiotensins, we established that 24 h of water deprivation resulted in an approximate 5-fold increase in the angiotensin release rate, whereas 48-h deprivation produced a dramatic 492-fold increase in release. Direct infusion of 65 mM K+ into the PVN was unable to stimulate angiotensin release, but 80 microM veratridine elicited a sevenfold increase in the angiotensin release rate. High-performance liquid chromatographic separation and RIA analysis of veratridine- and water deprivation-stimulated angiotensin release demonstrated that 93.4% of the releasable angiotensin coeluted with ANG III, whereas only 6.8% eluted with authentic ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)
已知脑内血管紧张素（ANG II和III）系统在心血管功能的中枢控制和机体水稳态中发挥重要作用。血管紧张素系统的许多成分，包括活性肽、前体、合成酶和受体，已定位到特定的脑核，如下丘脑室旁核（PVN）。我们和其他人推测，PVN是中枢血管紧张素系统的主要整合枢纽，它接收来自中枢探测器（室周器官）的血管紧张素能输入，并向更高的脑和脊髓中枢发送传出信号。这个观点隐含的意思是，血管紧张素与所有神经递质一样，应能在适当的化学和生理刺激下释放。因此，我们研究了禁水或直接注入65 mM K+或80 μM藜芦碱刺激大鼠PVN释放血管紧张素的能力。使用推挽式插管灌注PVN，并采用放射免疫分析法（RIA）分析超滤液中的免疫反应性血管紧张素，我们发现禁水24小时导致血管紧张素释放率增加约5倍，而禁水48小时则使释放量急剧增加492倍。向PVN直接注入65 mM K+无法刺激血管紧张素释放，但80 μM藜芦碱使血管紧张素释放率增加了7倍。对藜芦碱和禁水刺激的血管紧张素释放进行高效液相色谱分离和RIA分析表明，可释放的血管紧张素中有93.4%与ANG III共洗脱，而只有6.8%与 authentic ANG II共洗脱。（摘要截短为250字）
