Am J Nephrol. 2010;32(3):194-200. doi: 10.1159/000316528. Epub 2010 Jul 15.
To test the hypothesis that transient receptor potential vanilloid type 1 channel (TRPV1)-mediated increases in afferent renal nerve activity (ARNA) and release of substance P (SP) and calcitonin gene-related peptide (CGRP) from the renal pelvis are suppressed in Dahl salt-sensitive (DS), but not -resistant (DR), rats fed a high-salt (HS) diet.
Male DS and DR rats were given a HS or low-salt (LS) diet for 3 weeks. Perfusion of capsaicin (CAP, 10(-6)M), a selective TRPV1 agonist, into the left renal pelvis increased ipsilateral ARNA in all groups, but with a smaller magnitude in DS-HS compared to other groups. CAP increased contralateral urine flow in all groups except DS-HS rats. CAP-induced release of SP and CGRP from the renal pelvis was less in DS-HS compared to other groups. Western blot showed that TRPV1 expression in the kidney decreased while expression of neurokinin 1 receptors increased in DS-HS compared to other groups.
TRPV1-mediated increases in ARNA and release of SP and CGRP in the renal pelvis are impaired in DS rats fed a HS diet, which can likely be attributed to suppressed TRPV1 expression in the kidney and contributes to increased salt sensitivity.
验证瞬时受体电位香草酸亚型 1 通道(TRPV1)介导的传入肾神经活动(ARNA)增加和物质 P(SP)及降钙素基因相关肽(CGRP)从肾盂释放的假设,即在给予高盐(HS)饮食时,Dahl 盐敏感(DS)大鼠而非盐抵抗(DR)大鼠的这种作用受到抑制。
雄性 DS 和 DR 大鼠给予 HS 或低盐(LS)饮食 3 周。将辣椒素(CAP,10(-6)M),一种选择性 TRPV1 激动剂,灌注到左侧肾盂会增加所有组的同侧 ARNA,但 DS-HS 组的幅度较小。CAP 增加了除 DS-HS 大鼠以外所有组的对侧尿量。与其他组相比,CAP 诱导的肾盂 SP 和 CGRP 释放减少。Western blot 显示,与其他组相比,DS-HS 组肾脏中的 TRPV1 表达减少,而神经激肽 1 受体的表达增加。
给予 HS 饮食的 DS 大鼠,肾盂中 TRPV1 介导的 ARNA 增加和 SP 和 CGRP 释放受损,这可能归因于肾脏中 TRPV1 表达的抑制,并导致盐敏感性增加。