School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia.
Ups J Med Sci. 2011 Mar;116(1):18-25. doi: 10.3109/03009734.2010.526723. Epub 2010 Nov 4.
This study examined the effect of renal sympathetic innervation on adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction in Wistar-Kyoto (WKY) rats.
Forty-eight WKY rats were treated with either losartan (10 mg/kg/day p.o.) or carvedilol (5 mg/kg/day p.o.) or a combination of them (10 mg/kg/day + 5 mg/kg/day p.o.) for 7 days. On day 8, the rats were anaesthetized, and renal vasoconstrictor experiments were carried out. A group of rats was subjected to acute unilateral renal denervation during the acute study. Changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by Ang II, noradrenaline (NA), and methoxamine (ME).
In normal animals, losartan decreased (P < 0.05) the renal vasoconstrictor response to Ang II but not to NA or ME. Carvedilol treatment, however, blunted (P < 0.05) the renal vasoconstrictor responses to Ang II and adrenergic agonists. Combination of losartan and carvedilol blunted (P < 0.05) the renal vasoconstrictor response to Ang II but augmented the responses to NA and ME (all P < 0.05). Interestingly, when denervated rats were treated with the same combination, there was a reduction (P < 0.05) in the renal vasoconstrictor responses to Ang II and adrenergic agonists.
Data suggest that the renal sympathetic nerve contributes to adrenergic agonist-mediated renal vasoconstrictions in normal rats. The data further indicate an interactive relationship between renin-angiotensin and sympathetic nervous systems in modulating adrenergically and Ang II-induced renal vasoconstriction in WKY rats.
本研究探讨了肾交感神经支配对 Wistar-Kyoto（WKY）大鼠肾上腺素能和血管紧张素 II（Ang II）诱导的肾血管收缩的影响。
48 只 WKY 大鼠分别给予氯沙坦（10 mg/kg/天 po）、卡维地洛（5 mg/kg/天 po）或两者联合（10 mg/kg/天+5 mg/kg/天 po）治疗 7 天。第 8 天，大鼠麻醉后进行肾血管收缩实验。一组大鼠在急性研究中接受单侧肾去神经支配。通过 Ang II、去甲肾上腺素（NA）和甲氧胺（ME）引起的肾血流量减少来确定肾血管收缩反应的变化。
在正常动物中，氯沙坦降低（P < 0.05）了 Ang II 引起的肾血管收缩反应，但对 NA 或 ME 无影响。然而，卡维地洛治疗使 Ang II 和肾上腺素能激动剂引起的肾血管收缩反应减弱（P < 0.05）。氯沙坦和卡维地洛联合治疗减弱（P < 0.05）了 Ang II 的肾血管收缩反应，但增强了对 NA 和 ME 的反应（均 P < 0.05）。有趣的是，当去神经大鼠用相同的联合治疗时，Ang II 和肾上腺素能激动剂引起的肾血管收缩反应减少（P < 0.05）。
数据表明，肾交感神经参与了正常大鼠肾上腺素能激动剂介导的肾血管收缩。数据进一步表明，肾素-血管紧张素和交感神经系统在调节 WKY 大鼠肾上腺素能和 Ang II 诱导的肾血管收缩方面存在相互作用关系。
