Li Jianping, Wang Donna H
Department of Medicine, Michigan State University, East Lansing, MI 48824, USA.
J Hypertens. 2003 Mar;21(3):577-82. doi: 10.1097/00004872-200303000-00024.
To test the hypothesis that sensory afferents are significant functional components in preventing salt-induced increases in blood pressure.
Neonatal Wistar rats were subcutaneously injected with 50 mg/kg capsaicin or vehicle on the first and second days of life. After weaning, male rats were divided into three groups and treated for 4 weeks with: control plus normal (0.5%, CON-NS) or high (4%, CON-HS) sodium diet, and capsaicin pretreatment plus HS diet (CAP-HS). Mean arterial pressure (MAP) and its response to bolus injection of calcitonin gene-related peptide (CGRP) and its antagonist, CGRP(8-37), were measured by carotid arterial catheterization. Radioimmunoassay was used to measure CGRP levels in plasma and dorsal root ganglia (DRG). Expression of components of the CGRP receptor, calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1), was determined by the use of Western blot analysis.
Baseline MAP was increased in CAP-HS compared with CON-HS and CON-NS rats, and it was higher in CON-HS than in CON-NS rats. MAP response to exogenous CGRP was enhanced in CAP-HS and CON-HS than in CON-NS rats, but MAP response to CGRP(8-37) was increased only in CON-HS rats. Plasma CGRP levels were not different among three groups, but CGRP content in DRG was decreased in CAP-HS compared with CON-HS and CON-NS rats. CRLR expression in mesenteric resistance arteries was upregulated in CAP-HS and CON-HS compared with CON-NS rats, but RAMP1 content was not different among these groups.
Chronic high-salt intake upregulates expression of mesenteric CGRP receptors without altering CGRP levels in plasma and DRG. Increased expression of mesenteric CGRP receptors may play a counter regulatory role in attenuating salt-induced increases in blood pressure.
验证感觉传入神经是预防盐诱导血压升高的重要功能组成部分这一假说。
新生Wistar大鼠在出生第1天和第2天皮下注射50mg/kg辣椒素或赋形剂。断奶后，将雄性大鼠分为三组，分别给予以下处理4周：对照组加正常（0.5%，CON-NS）或高（4%，CON-HS）钠饮食，以及辣椒素预处理加高钠饮食（CAP-HS）。通过颈动脉插管测量平均动脉压（MAP）及其对降钙素基因相关肽（CGRP）及其拮抗剂CGRP(8 - 37)推注的反应。采用放射免疫分析法测定血浆和背根神经节（DRG）中的CGRP水平。通过蛋白质免疫印迹分析确定CGRP受体成分、降钙素受体样受体（CRLR）和受体活性修饰蛋白1（RAMP1）的表达。
与CON-HS和CON-NS大鼠相比，CAP-HS大鼠的基线MAP升高，且CON-HS大鼠的基线MAP高于CON-NS大鼠。与CON-NS大鼠相比，CAP-HS和CON-HS大鼠对外源性CGRP的MAP反应增强，但仅CON-HS大鼠对CGRP(8 - 37)的MAP反应增加。三组间血浆CGRP水平无差异，但与CON-HS和CON-NS大鼠相比，CAP-HS大鼠DRG中的CGRP含量降低。与CON-NS大鼠相比，CAP-HS和CON-HS大鼠肠系膜阻力动脉中的CRLR表达上调，但这些组间的RAMP1含量无差异。
慢性高盐摄入上调肠系膜CGRP受体的表达，而不改变血浆和DRG中的CGRP水平。肠系膜CGRP受体表达增加可能在减轻盐诱导的血压升高中起反向调节作用。
