Kopp Ulla C, Cicha Michael Z, Smith Lori A
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, USA.
Hypertension. 2007 Jan;49(1):141-7. doi: 10.1161/01.HYP.0000249634.46212.7b. Epub 2006 Oct 23.
Activation of renal mechanosensory nerves is enhanced by a high-sodium diet and suppressed by a low-sodium diet. Angiotensin (Ang) II and endothelin (ET)-1 each contributes to the impaired responsiveness of renal mechanosensory nerves in a low-sodium diet. We examined whether stimulation of ETA receptors (Rs) contributes to Ang II-induced suppression of the responsiveness of renal mechanosensory nerves. In anesthetized rats fed a low-sodium diet, renal pelvic administration of the Ang type I receptor (AT1-R) antagonist losartan enhanced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mm Hg from 7+/-2% to 15+/-2% and the prostaglandin (PG) E(2)-mediated substance P release from 0+/-1 to 8+/-1 pg/min. Adding the ETA-R antagonist BQ123 to the renal pelvic perfusate containing losartan did not produce any further enhancement of the ARNA response or PGE(2)-mediated release of substance P (17+/-3% and 8+/-1 pg/min). Likewise, renal pelvic administration of BQ123 and BQ123+losartan resulted in similar enhancements of the ARNA responses to increased renal pelvic pressure and PGE(2)-mediated substance P release. In high-sodium-diet rats, pelvic administration of Ang II reduced the ARNA response to increased renal pelvic pressure from 27+/-4% to 8+/-3% and the PGE(2)-mediated substance P release from 9+/-0 to 1+/-1 pg/min. Adding BQ123 to the renal pelvic perfusate containing Ang II restored the increases in ARNA and the PGE(2)-mediated substance P release toward control (27+/-6% and 7+/-1 pg/min). In conclusion, stimulation of ETA-R plays an important contributory role to the Ang II-mediated suppression of the activation of renal mechanosensory nerves in conditions of low-sodium diet.
高钠饮食可增强肾机械感觉神经的激活，而低钠饮食则抑制其激活。血管紧张素（Ang）II和内皮素（ET）-1均导致低钠饮食时肾机械感觉神经反应性受损。我们研究了刺激ETA受体（Rs）是否有助于Ang II诱导的肾机械感觉神经反应性抑制。在喂食低钠饮食的麻醉大鼠中，经肾盂给予血管紧张素I型受体（AT1-R）拮抗剂氯沙坦可增强肾传入神经活动（ARNA）对肾盂压力从7.5毫米汞柱增加到7±2%至15±2%的反应，以及前列腺素（PG）E2介导的P物质释放从0±1增加到8±1皮克/分钟。在含有氯沙坦的肾盂灌注液中加入ETA-R拮抗剂BQ123，并未进一步增强ARNA反应或PGE2介导的P物质释放（分别为17±3%和8±1皮克/分钟）。同样，经肾盂给予BQ123和BQ123+氯沙坦，对肾盂压力增加引起的ARNA反应和PGE2介导的P物质释放有类似的增强作用。在高钠饮食的大鼠中，经肾盂给予Ang II可使ARNA对肾盂压力增加的反应从27±4%降至8±3%，PGE2介导的P物质释放从9±0降至1±1皮克/分钟。在含有Ang II的肾盂灌注液中加入BQ123可使ARNA和PGE2介导的P物质释放恢复至对照水平（分别为27±6%和7±1皮克/分钟）。总之，在低钠饮食条件下，刺激ETA-R在Ang II介导的肾机械感觉神经激活抑制中起重要作用。
