Kopp Ulla C, Cicha Michael Z, Smith Lori A
Dept. of Internal Medicine, VA Medical Center, University of Iowa Carver College of Medicine, Bldg. 3, Rm. 226, Highway 6W, Iowa City, IA 52246, USA.
Am J Physiol Regul Integr Comp Physiol. 2006 Nov;291(5):R1545-56. doi: 10.1152/ajpregu.00878.2005. Epub 2006 Jun 8.
Activation of renal mechanosensory nerves is enhanced by high and suppressed by low sodium dietary intake. Afferent renal denervation results in salt-sensitive hypertension, suggesting that activation of the afferent renal nerves contributes to water and sodium balance. Another model of salt-sensitive hypertension is the endothelin B receptor (ETBR)-deficient rat. ET and its receptors are present in sensory nerves. Therefore, we examined whether ET receptor blockade altered the responsiveness of the renal sensory nerves. In anesthetized rats fed high-sodium diet, renal pelvic administration of the ETBR antagonist BQ-788 reduced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mmHg from 26+/-3 to 9+/-3% and the PGE2-mediated renal pelvic release of substance P from 9+/-1 to 3+/-1 pg/min. Conversely, in rats fed low-sodium diet, renal pelvic administration of the ETAR antagonist BQ-123 enhanced the ARNA response to increased renal pelvic pressure from 9+/-2 to 23+/-6% and the PGE2-mediated renal pelvic release of substance P from 0+/-0 to 6+/-1 pg/min. Adding the ETAR antagonist to ETBR-blocked renal pelvises restored the responsiveness of renal sensory nerves in rats fed a high-sodium diet. Adding the ETBR antagonist to ETAR-blocked pelvises suppressed the responsiveness of the renal sensory nerves in rats fed a low-sodium diet. In conclusion, activation of ETBR and ETAR contributes to the enhanced and suppressed responsiveness of renal sensory nerves in conditions of high- and low-sodium dietary intake, respectively. Impaired renorenal reflexes may contribute to the salt-sensitive hypertension in the ETBR-deficient rat.
高钠饮食可增强肾机械感觉神经的激活，而低钠饮食则抑制这种激活。肾传入神经去神经支配会导致盐敏感性高血压，这表明肾传入神经的激活有助于水和钠平衡。盐敏感性高血压的另一个模型是内皮素B受体（ETBR）缺陷大鼠。ET及其受体存在于感觉神经中。因此，我们研究了ET受体阻断是否会改变肾感觉神经的反应性。在喂食高钠饮食的麻醉大鼠中，经肾盂给予ETBR拮抗剂BQ-788可使肾传入神经活动（ARNA）对肾盂压力从26±3 mmHg升高7.5 mmHg的反应从26±3%降至9±3%，并使PGE2介导的肾盂P物质释放从9±1 pg/min降至3±1 pg/min。相反，在喂食低钠饮食的大鼠中，经肾盂给予ETAR拮抗剂BQ-123可使ARNA对肾盂压力升高的反应从9±2%增强至23±6%，并使PGE2介导的肾盂P物质释放从0±0 pg/min增至6±1 pg/min。在喂食高钠饮食的大鼠中，将ETAR拮抗剂添加到被ETBR阻断的肾盂中可恢复肾感觉神经的反应性。在喂食低钠饮食的大鼠中，将ETBR拮抗剂添加到被ETAR阻断的肾盂中可抑制肾感觉神经的反应性。总之，ETBR和ETAR的激活分别导致在高钠和低钠饮食条件下肾感觉神经反应性的增强和抑制。肾肾反射受损可能导致ETBR缺陷大鼠出现盐敏感性高血压。
