Intrahypothalamic secretion of angiotensin II in response to immunological or non-immunological stress in rats : a microdialysis study

我们先前报道脑血管紧张素II(Ang II)受体参与免疫或非免疫应激引起的大鼠发热。采用微透析技术，观察免疫性应激(前列腺素E_2(PGE_2)注射)或非免疫性(制动)应激对大鼠下丘脑血管紧张素Ⅱ(Ang II)分泌的影响。我们的微透析研究(灌流速度=2μL/分钟，恢复率=14.2%)表明，在下丘脑内灌流前列腺素E_2(2μ/2μL灌流液/分钟)时，可通过灌流液中含有少量的血管紧张素Ⅱ而检测到下丘脑血管紧张素Ⅱ的释放(平均0.17pg/2μL灌流液/分钟；n=3)。在车辆输液过程中(n=4)，血管紧张素Ⅱ的释放没有发生。因此，有理由认为下丘脑中的PGE_2与下丘脑内的PGE受体结合，从而导致Ang II的释放。随后，下丘脑内释放的Ang II可能对PGE_2引起的发热反应进行了调制。相反，当大鼠暴露于束缚应激时，大鼠下丘脑中未检测到Ang II的分泌。由于本研究中使用的微透析探头的回收率为14.2%，而且多肽非常不稳定，因此可能无法测量到Ang II的实际分泌。为了检测如此少量的多肽，例如通过使用使多肽失活的酶的抑制剂，技术改进是必要的。

We previously reported that brain angiotensin II (ANG II) receptors contribute to the fever induced by immunological or non-immunological stress in rats. The present study was carried out to investigate whether immunological [prostaglandin E_2 (PGE_2) injection] or non-immunological (immobilization) stress elicits the secretion of ANG II in the hypothalamus in rats, using microdialysis technique. Our microdialysis study (perfusion flow rate=2 μl/min and recovery rate=14.2%) showed that, during intrahypothalamic perfusion with PGE_2 (2 μg/2 μl perfusate/min), ANG II release in the hypothalamus could be detected by the presence of a small amount of ANG II in the perfusate (on average, 0.17 pg/2 μl perfusate/min ; n=3). Such a release of ANG II did not occur during vehicle infusion (n=4). It is therefore reasonable to consider that PGE_2 in the hypothalamus binds to intrahypothalamic PGE receptors, which results in ANG II release. Subsequently, ANG II released within the hypothalamus might modulate the PGE_2-induced febrile responses. In contrast, when rats were exposed to immobilization stress, no secretion of ANG II was detected in the rat's hypothalamus. Since the recovery rate of the microdialysis probe used in this study was 14.2% and the peptide is so unstable, actual secretion of ANG II might have been unable to be measured. Technical improvement is necessary to detect such a small amount of the peptide, for example by using the inhibitors of the enzyme which inactivates the peptide.