Hobara Narumi, Goda Mitsuhiro, Hashikawa Naoya, Jin Xin, Zamami Yoshito, Takatori Shingo, Kawasaki Hiromu
Department of Life Science, Okayama University of Science, Okayama, Japan.
Yakugaku Zasshi. 2010 Nov;130(11):1421-5. doi: 10.1248/yakushi.130.1421.
The aim of this study was to investigate age-related changes in the density of calcitonin gene-related peptide (CGRP)-containing nerve fibers in spontaneously hypertensive rats (SHR) and the effects of long-term inhibition of the renin-angiotensin system on these changes. An age-related decrease in the density of CGRP-like immunoreactive (LI)-containing nerve fibers but not neuropeptide Y (NPY)-LI-containing sympathetic nerve fibers was found in the mesenteric artery of SHR but not Wistar-Kyoto rats (WKY). The density of NPY-LI-containing nerve fibers was significantly greater in SHR than in WKY. SHR were treated for 7 weeks with angiotensin-converting enzyme inhibitor (0.005% temocapril), angiotensin II type-1 (AT1) receptor antagonist (0.025% losartan), or vasodilator (0.01% hydralazine) in their drinking water. Each drug treatment significantly lowered the systolic blood pressure measured using the tail-cuff method. Long-term treatment of SHR with temocapril and losartan significantly increased the density of CGRP-LI-containing nerve fibers in mesenteric arteries. Furthermore, to clarify the effect of the angiontensin II type-2 (AT2) receptor in the restoration of perivascular nerve innervation, we used the phenol-injured rat model, in which the perivascular nerves are markedly reduced by the topical application of phenol. Activation of AT2R significantly restored CGRP-LI innervation in phenol-injured rats. These results suggest that selective stimulation of AT2 receptors facilitates reinnervation of mesenteric perivascular CGRP-containing nerves.
本研究旨在探讨自发性高血压大鼠（SHR）中降钙素基因相关肽（CGRP）阳性神经纤维密度的年龄相关变化，以及长期抑制肾素-血管紧张素系统对这些变化的影响。在SHR的肠系膜动脉中发现了含CGRP样免疫反应性（LI）神经纤维密度的年龄相关下降，但在Wistar-Kyoto大鼠（WKY）中未发现，而含神经肽Y（NPY）-LI的交感神经纤维密度在SHR中未出现这种下降。SHR中含NPY-LI神经纤维的密度显著高于WKY。给SHR在饮水中给予血管紧张素转换酶抑制剂（0.005%替莫卡普利）、血管紧张素II 1型（AT1）受体拮抗剂（0.025%氯沙坦）或血管扩张剂（0.01%肼屈嗪）治疗7周。每种药物治疗均显著降低了用尾袖法测量的收缩压。替莫卡普利和氯沙坦对SHR的长期治疗显著增加了肠系膜动脉中含CGRP-LI神经纤维的密度。此外，为了阐明血管紧张素II 2型（AT2）受体在恢复血管周围神经支配中的作用，我们使用了苯酚损伤大鼠模型，在该模型中，通过局部应用苯酚可使血管周围神经明显减少。激活AT2R可显著恢复苯酚损伤大鼠的CGRP-LI神经支配。这些结果表明，选择性刺激AT2受体有助于肠系膜血管周围含CGRP神经的再支配。
