Galligan James J, Miller Sara B, Katki Khurshed, Supowit Scott, DiPette Donald, Fink Gregory D
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Regul Pept. 2006 Jan 15;133(1-3):97-104. doi: 10.1016/j.regpep.2005.09.030. Epub 2005 Nov 17.
This study examined sensory nerves associated with mesenteric arteries and veins in sham and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Reactivity of arteries and veins to substances released from sensory nerves was also studied in vitro using computer-assisted video microscopy. Co-localization of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactivity (ir) was used to evaluate perivascular sensory nerves. Radioimmunoassay was used to quantify SP- and CGRP-ir content. Immunohistochemical studies revealed a plexus of SP/CGRP-ir nerves associated with arteries and veins. The intensity of SP-ir, but not CGRP-ir labeling was greater in arteries and veins from DOCA-salt compared to sham rats. RIA measurements revealed that the CGRP-ir content of arteries and veins was higher than the SP-ir content but there was a significant increase in SP-ir, but not CGRP-ir, content in arteries and veins from DOCA-salt rats. SP (0.03-1 microM) contracted veins and the NK-3 receptor agonist, senktide, mimicked this effect. There were no differences in SP or senktide reactivity of veins from sham or DOCA-salt rats. SP, but not senktide, relaxed KCl (40 mM) preconstricted arteries. CGRP (0.3 microM), acetylcholine (10 microM) and capsaicin (1 microM) relaxed KCl-preconstricted arteries and veins. The NK-1 receptor agonist, substance P methyl ester relaxed arteries but not veins. These data indicate that DOCA-salt hypertension is associated with upregulation of SP content in perivascular nerves. NK-3 receptors mediate venoconstriction which is unchanged in DOCA-salt hypertension. Increased release of SP from perivenous nerves might contribute to the increased venomotor tone in DOCA-salt hypertension.
本研究检测了假手术组和醋酸脱氧皮质酮（DOCA）-盐诱导的高血压大鼠肠系膜动静脉相关的感觉神经。还使用计算机辅助视频显微镜在体外研究了动静脉对感觉神经释放物质的反应性。采用P物质（SP）和降钙素基因相关肽（CGRP）免疫反应性（ir）的共定位来评估血管周围感觉神经。放射免疫分析法用于定量SP-ir和CGRP-ir含量。免疫组织化学研究显示，与动静脉相关的有一个SP/CGRP-ir神经丛。与假手术组大鼠相比，DOCA-盐组大鼠动静脉中SP-ir的强度增加，但CGRP-ir标记强度未增加。放射免疫分析测量显示，动静脉的CGRP-ir含量高于SP-ir含量，但DOCA-盐组大鼠动静脉中SP-ir含量显著增加，而CGRP-ir含量未增加。SP（0.03-1微摩尔）使静脉收缩，NK-3受体激动剂森克肽模拟了这种作用。假手术组或DOCA-盐组大鼠静脉对SP或森克肽的反应性没有差异。SP可使氯化钾（40毫摩尔）预收缩的动脉舒张，但森克肽不能。CGRP（0.3微摩尔）、乙酰胆碱（10微摩尔）和辣椒素（1微摩尔）可使氯化钾预收缩的动静脉舒张。NK-1受体激动剂P物质甲酯可使动脉舒张，但不能使静脉舒张。这些数据表明，DOCA-盐性高血压与血管周围神经中SP含量上调有关。NK-3受体介导静脉收缩，在DOCA-盐性高血压中无变化。静脉周围神经释放SP增加可能导致DOCA-盐性高血压中静脉活动张力增加。
