Dept. of Internal Medicine, Department of Veterans Affairs Medical Center, Bldg. 41, Highway 6W, Iowa City, IA 52246, USA.
Am J Physiol Regul Integr Comp Physiol. 2011 Feb;300(2):R298-310. doi: 10.1152/ajpregu.00469.2010. Epub 2010 Nov 24.
Activation of efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which then reflexively decreases ERSNA via activation of the renorenal reflexes to maintain low ERSNA. The ERSNA-ARNA interaction is mediated by norepinephrine (NE) that increases and decreases ARNA by activation of renal α(1)-and α(2)-adrenoceptors (AR), respectively. The ERSNA-induced increases in ARNA are suppressed during a low-sodium (2,470 ± 770% s) and enhanced during a high-sodium diet (5,670 ± 1,260% s). We examined the role of α(2)-AR in modulating the responsiveness of renal sensory nerves during low- and high-sodium diets. Immunohistochemical analysis suggested the presence of α(2A)-AR and α(2C)-AR subtypes on renal sensory nerves. During the low-sodium diet, renal pelvic administration of the α(2)-AR antagonist rauwolscine or the AT1 receptor antagonist losartan alone failed to alter the ARNA responses to reflex increases in ERSNA. Likewise, renal pelvic release of substance P produced by 250 pM NE (from 8.0 ± 1.3 to 8.5 ± 1.6 pg/min) was not affected by rauwolscine or losartan alone. However, rauwolscine+losartan enhanced the ARNA responses to reflex increases in ERSNA (4,680 ± 1,240%·s), and renal pelvic release of substance P by 250 pM NE, from 8.3 ± 0.6 to 14.2 ± 0.8 pg/min. During a high-sodium diet, rauwolscine had no effect on the ARNA response to reflex increases in ERSNA or renal pelvic release of substance P produced by NE. Losartan was not examined because of low endogenous ANG II levels in renal pelvic tissue during a high-sodium diet. Increased activation of α(2)-AR contributes to the reduced interaction between ERSNA and ARNA during low-sodium intake, whereas no/minimal activation of α(2)-AR contributes to the enhanced ERSNA-ARNA interaction under conditions of high sodium intake.
传出肾交感神经活动(ERSNA)的激活会增加传入肾神经活动(ARNA),然后通过激活肾肾反射来反射性地降低 ERSNA,以维持低 ERSNA。ERSNA-ARNA 相互作用是由去甲肾上腺素(NE)介导的,它通过激活肾 α(1)-和 α(2)-肾上腺素受体(AR)分别增加和减少 ARNA。在低钠饮食(2,470 ± 770% s)期间,ERSNA 诱导的 ARNA 增加受到抑制,而在高钠饮食期间(5,670 ± 1,260% s)则增强。我们检查了 α(2)-AR 在调节低钠和高钠饮食期间肾感觉神经反应性中的作用。免疫组织化学分析表明,肾感觉神经上存在 α(2A)-AR 和 α(2C)-AR 亚型。在低钠饮食期间,肾集合管给予 α(2)-AR 拮抗剂 rauwolscine 或 AT1 受体拮抗剂 losartan 单独不能改变对 ERSNA 反射性增加的 ARNA 反应。同样,由 250 pM NE 产生的肾集合管释放的 P 物质(从 8.0 ± 1.3 到 8.5 ± 1.6 pg/min)不受 rauwolscine 或 losartan 单独的影响。然而,rauwolscine+losartan 增强了对 ERSNA 反射性增加的 ARNA 反应(4,680 ± 1,240%·s),并且由 250 pM NE 产生的肾集合管释放的 P 物质从 8.3 ± 0.6 增加到 14.2 ± 0.8 pg/min。在高钠饮食期间,rauwolscine 对 ERSNA 反射性增加引起的 ARNA 反应或由 NE 产生的肾集合管释放 P 物质没有影响。由于高钠饮食期间肾集合管组织中内源性 ANG II 水平较低,因此未检查 losartan。α(2)-AR 的激活增加有助于在低钠摄入期间降低 ERSNA 与 ARNA 之间的相互作用,而在高钠摄入条件下,α(2)-AR 的最小/无激活有助于增强 ERSNA-ARNA 相互作用。