Kawasaki Hiromu, Inaizumi Keiichi, Nakamura Arisa, Hobara Narumi, Kurosaki Yuji
Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka, Okayama, Japan.
Hypertens Res. 2003 Mar;26(3):257-63. doi: 10.1291/hypres.26.257.
We previously reported that the vasodilation mediated by calcitonin gene-related peptide (CGRP)-containing nerves and level of CGRP mRNA in the dorsal root ganglia (DRG) in spontaneously hypertensive rats (SHR) decreased with age, and that the reduced function of CGRP nerves was restored by chronic inhibition of angiotensin II. The present study was performed to investigate the effect of long-term treatment with angiotensin II type-1 receptor antagonists (L-158,809 and olmesartan), an angiotensin converting enzyme inhibitor (temocapril) and hydralazine on levels of CGRP mRNA in DRG of SHR and the contents of CGRP in the mesenteric artery and atrium. The level of CGRP mRNA and degree of CGRP-like immunoreactivities (CGRP-LI) were measured by Northern blot hybridization assay and enzyme-linked immunosorbent assay, respectively. Seven week-treatment of 8 week-old SHR with temocapril (0.005%), L-158,809 (0.001%), olmesartan (0.01%) or hydralazine (0.01%) administered in drinking water significantly lowered the systolic blood pressure of SHR. The level of CGRP mRNA in the DRG of control SHR was significantly lower than that in normotensive Wistar Kyoto rats (WKY), whereas the level of CGRP-LI in the mesenteric artery and atrium of SHR were significantly greater than those in WKY. Treatment of SHR with temocapril, L-158,809, or olmesartan, but not hydralazine, significantly elevated the levels of CGRP mRNA in DRG, markedly increased the level of CGRP-LI in the mesenteric artery, and slightly increased the CGRP-LI level in the atrium. These results suggest that long-term inhibition of angiotensin II restores the reduced expression of CGRP mRNA in DRG and may facilitate neurotransmission of CGRP-containing vasodilator nerves in SHR.
我们之前报道过，自发性高血压大鼠（SHR）中，含降钙素基因相关肽（CGRP）的神经介导的血管舒张以及背根神经节（DRG）中CGRP mRNA的水平会随年龄增长而降低，并且通过长期抑制血管紧张素II可恢复CGRP神经功能的减退。本研究旨在探讨血管紧张素II 1型受体拮抗剂（L-158,809和奥美沙坦）、血管紧张素转换酶抑制剂（替莫卡普利）和肼屈嗪长期治疗对SHR的DRG中CGRP mRNA水平以及肠系膜动脉和心房中CGRP含量的影响。分别通过Northern印迹杂交分析和酶联免疫吸附测定法测量CGRP mRNA水平和CGRP样免疫反应性（CGRP-LI）程度。用替莫卡普利（0.005%）、L-158,809（0.001%）、奥美沙坦（0.01%）或肼屈嗪（0.01%）对8周龄SHR进行为期7周的饮水给药，可显著降低SHR的收缩压。对照SHR的DRG中CGRP mRNA水平显著低于正常血压的Wistar Kyoto大鼠（WKY），而SHR的肠系膜动脉和心房中的CGRP-LI水平显著高于WKY。用替莫卡普利、L-158,809或奥美沙坦治疗SHR，但不包括肼屈嗪，可显著提高DRG中CGRP mRNA水平，显著增加肠系膜动脉中CGRP-LI水平，并略微增加心房中CGRP-LI水平。这些结果表明，长期抑制血管紧张素II可恢复SHR的DRG中CGRP mRNA表达的降低，并可能促进含CGRP的血管舒张神经的神经传递。
