Kopp Ulla C, Cicha Michael Z, Yorek Mark A
Department of Internal Medicine, Department of Veterans Affairs Medical Center, Bldg. 41, Rm 124, Highway 6W, Iowa City, IA 52246, USA.
Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R858-66. doi: 10.1152/ajpregu.00830.2007. Epub 2008 Jan 16.
Increasing afferent renal nerve activity decreases efferent renal nerve activity and increases urinary sodium excretion. Activation of renal pelvic mechanosensory nerves is impaired in streptozotocin (STZ)-treated rats (model of type 1 diabetes). Decreased activation of renal sensory nerves would lead to increased efferent renal nerve activity, sodium retention, and hypertension. We examined whether the reduced activation of renal sensory nerves in STZ rats was due to increased renal angiotensin activity and whether activation of the renal sensory nerves was impaired in obese Zucker diabetic fatty (ZDF) rats (model of type 2 diabetes). In an isolated renal pelvic wall preparation from rats treated with STZ for 2 wk, PGE2 failed to increase the release of substance P, from 5 +/- 1 to 6 +/- 1 pg/min. In pelvises from sham STZ rats, PGE2 increased substance P release from 6 +/- 1 to 13 +/- 2 pg/min. Adding losartan to the incubation bath increased PGE2-mediated release of substance P in STZ rats, from 5 +/- 1 to 10 +/- 2 pg/min, but had no effect in sham STZ rats. In pelvises from obese ZDF rats (22-46 wk old), PGE2 increased substance P release from 12.0 +/- 1.2 to 18.3 +/- 1.2 pg/min, which was less than that from lean ZDF rats (10.3 +/- 1.6 to 22.5 +/- 2.4 pg/min). Losartan had no effect on the PGE2-mediated substance P release in obese or lean ZDF rats. We conclude that the mechanisms involved in the decreased responsiveness of the renal sensory nerves in STZ rats involve activation of the renin angiotensin system in STZ but not in obese ZDF rats.
肾传入神经活动增强会降低肾传出神经活动并增加尿钠排泄。链脲佐菌素（STZ）处理的大鼠（1型糖尿病模型）肾盂机械感觉神经的激活受损。肾感觉神经激活减少会导致肾传出神经活动增加、钠潴留和高血压。我们研究了STZ大鼠肾感觉神经激活减少是否归因于肾血管紧张素活性增加，以及肥胖Zucker糖尿病脂肪（ZDF）大鼠（2型糖尿病模型）的肾感觉神经激活是否受损。在用STZ处理2周的大鼠分离的肾盂壁制备物中，前列腺素E2（PGE2）未能使P物质释放增加，从5±1皮克/分钟增加到6±1皮克/分钟。在假手术STZ大鼠的肾盂中，PGE2使P物质释放从6±1皮克/分钟增加到13±2皮克/分钟。在孵育浴中加入氯沙坦可增加STZ大鼠中PGE2介导的P物质释放，从5±1皮克/分钟增加到10±2皮克/分钟，但对假手术STZ大鼠无影响。在肥胖ZDF大鼠（22 - 46周龄）的肾盂中，PGE2使P物质释放从12.0±1.2皮克/分钟增加到18.3±1.2皮克/分钟，低于瘦ZDF大鼠（10.3±1.6皮克/分钟增加到22.5±2.4皮克/分钟）。氯沙坦对肥胖或瘦ZDF大鼠中PGE2介导的P物质释放均无影响。我们得出结论，STZ大鼠肾感觉神经反应性降低所涉及的机制在STZ大鼠中涉及肾素血管紧张素系统的激活，但在肥胖ZDF大鼠中并非如此。
