Kopp Ulla C, Cicha Michael Z, Smith Lori A, Mulder Jan, Hökfelt Tomas
Dept. of Internal Medicine, VA Medical Center, Bldg. 41, Rm 124, Highway 6W, Iowa City, IA 52246, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Oct;293(4):R1561-72. doi: 10.1152/ajpregu.00485.2007. Epub 2007 Aug 15.
Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA). To test whether the ERSNA-induced increases in ARNA involved norepinephrine activating alpha-adrenoceptors on the renal sensory nerves, we examined the effects of renal pelvic administration of the alpha(1)- and alpha(2)-adrenoceptor antagonists prazosin and rauwolscine on the ARNA responses to reflex increases in ERSNA (placing the rat's tail in 49 degrees C water) and renal pelvic perfusion with norepinephrine in anesthetized rats. Hot tail increased ERSNA and ARNA, 6,930 +/- 900 and 4,870 +/- 670%.s (area under the curve ARNA vs. time). Renal pelvic perfusion with norepinephrine increased ARNA 1,870 +/- 210%.s. Immunohistochemical studies showed that the sympathetic and sensory nerves were closely related in the pelvic wall. Renal pelvic perfusion with prazosin blocked and rauwolscine enhanced the ARNA responses to reflex increases in ERSNA and norepinephrine. Studies in a denervated renal pelvic wall preparation showed that norepinephrine increased substance P release, from 8 +/- 1 to 16 +/- 1 pg/min, and PGE(2) release, from 77 +/- 11 to 161 +/- 23 pg/min, suggesting a role for PGE(2) in the norepinephrine-induced activation of renal sensory nerves. Prazosin and indomethacin reduced and rauwolscine enhanced the norepinephrine-induced increases in substance P and PGE(2). PGE(2) enhanced the norepinephrine-induced activation of renal sensory nerves by stimulation of EP4 receptors. Interaction between ERSNA and ARNA is modulated by norepinephrine, which increases and decreases the activation of the renal sensory nerves by stimulating alpha(1)- and alpha(2)-adrenoceptors, respectively, on the renal pelvic sensory nerve fibers. Norepinephrine-induced activation of the sensory nerves is dependent on renal pelvic synthesis/release of PGE(2).
肾传出交感神经活动（ERSNA）增强会使肾传入神经活动（ARNA）增加。为了检验ERSNA诱导的ARNA增加是否涉及去甲肾上腺素激活肾感觉神经上的α-肾上腺素能受体，我们研究了肾盂注射α₁-和α₂-肾上腺素能受体拮抗剂哌唑嗪和萝芙木碱对ARNA对ERSNA反射性增加（将大鼠尾巴置于49℃水中）及肾盂灌注去甲肾上腺素的反应的影响，实验对象为麻醉大鼠。热尾巴使ERSNA和ARNA增加，分别为6930±900%·s和4870±670%·s（ARNA曲线下面积与时间）。肾盂灌注去甲肾上腺素使ARNA增加1870±210%·s。免疫组织化学研究表明，交感神经和感觉神经在肾盂壁紧密相连。肾盂灌注哌唑嗪可阻断，而萝芙木碱可增强ARNA对ERSNA反射性增加及去甲肾上腺素的反应。在去神经支配的肾盂壁标本中的研究表明，去甲肾上腺素使P物质释放从8±1 pg/min增加到16±1 pg/min，PGE₂释放从77±11 pg/min增加到161±23 pg/min，提示PGE₂在去甲肾上腺素诱导的肾感觉神经激活中起作用。哌唑嗪和吲哚美辛可减少，而萝芙木碱可增强去甲肾上腺素诱导的P物质和PGE₂增加。PGE₂通过刺激EP4受体增强去甲肾上腺素诱导的肾感觉神经激活。ERSNA和ARNA之间的相互作用由去甲肾上腺素调节，去甲肾上腺素分别通过刺激肾盂感觉神经纤维上的α₁-和α₂-肾上腺素能受体增加和减少肾感觉神经的激活。去甲肾上腺素诱导的感觉神经激活依赖于肾盂PGE₂的合成/释放。
