Department of Biomedical Sciences, University of Copenhagen, Denmark.
Acta Physiol (Oxf). 2012 Mar;204(3):451-9. doi: 10.1111/j.1748-1716.2011.02351.x. Epub 2011 Sep 27.
Congestive heart failure (CHF) is associated with increased renal sympathetic nerve activity and renal sodium retention. Rats with CHF display increased expression of the Na-K-2Cl cotransporter (NKCC2) in the renal medullary thick ascending limb of the loop of Henle (mTAL), and arginine vasopressin (AVP)-stimulated cAMP formation in mTAL segments is increased in rats with CHF. The aim of the study was to investigate the role of RSNA on cAMP formation and NKCC2 expression in mTAL in rats with CHF.
Congestive heart failure was induced in male Wistar rats by ligation of the left anterior descending coronary artery. Bilateral surgical renal denervation (DNX) was performed 3 weeks later. Two weeks after DNX, mTAL segments were isolated and stimulated with AVP.
Congestive heart failure rats displayed increased mTAL NKCC2 expression (2.5 ± 0.5 vs. 1 ± 0.2 in Sham rats), which was abolished by DNX. Bilateral denervation decreased basal cAMP levels in unstimulated tubules from CHF rats (CHF: 12.56 ± 7.73 fmol μg(-1) protein vs. DNX-CHF: 7.94 ± 4.33; P < 0.05), as well as from Sham rats (SHAM: 4.70 ± 1.38 vs. DNX-SHAM: 2.36 ± 1.52; P < 0.05). mTAL segments from DNX-CHF and DNX-Sham rats showed decreased AVP (10(-6) M)-stimulated cAMP formation, compared with CHF (CHF: 11.92 ± 4.89 fmol μg(-1) protein vs. DNX-CHF: 4.68 ± 2.47; P < 0.05) and Sham (SHAM: 10.78 ± 5.59 vs. DNX-SHAM: 4.89 ± 2.62; P < 0.05).
These results indicate that the renal sympathetic nerves have an effect on NKCC2 expression in the mTAL and might have an effect on cAMP formation in the TAL in CHF.
充血性心力衰竭（CHF）与肾交感神经活动增加和肾钠潴留有关。患有 CHF 的大鼠在肾脏髓质升支粗段的升支粗段（mTAL）中显示出 Na-K-2Cl 共转运蛋白（NKCC2）表达增加，并且 CHF 大鼠的 mTAL 段中 AVP 刺激的 cAMP 形成增加。本研究的目的是探讨 RSNA 在 CHF 大鼠 mTAL 中 cAMP 形成和 NKCC2 表达中的作用。
通过结扎左前降支冠状动脉诱导雄性 Wistar 大鼠充血性心力衰竭。3 周后进行双侧外科肾去神经支配（DNX）。DNX 后 2 周，分离 mTAL 段并用 AVP 刺激。
充血性心力衰竭大鼠显示 mTAL NKCC2 表达增加（2.5 ± 0.5 比 Sham 大鼠的 1 ± 0.2），DNX 可消除这种增加。双侧去神经支配降低了 CHF 大鼠未刺激管段的基础 cAMP 水平（CHF：12.56 ± 7.73 fmol/μg 蛋白比 DNX-CHF：7.94 ± 4.33; P < 0.05），以及 Sham 大鼠（SHAM：4.70 ± 1.38 比 DNX-SHAM：2.36 ± 1.52; P < 0.05）。与 CHF 大鼠（CHF：11.92 ± 4.89 fmol/μg 蛋白比 DNX-CHF：4.68 ± 2.47; P < 0.05）和 Sham 大鼠（SHAM：10.78 ± 5.59 比 DNX-SHAM：4.89 ± 2.62; P < 0.05）相比，DNX-CHF 和 DNX-Sham 大鼠的 mTAL 段对 AVP（10（-6）M）刺激的 cAMP 形成减少。
这些结果表明，肾交感神经对 mTAL 中的 NKCC2 表达有影响，并且可能对 CHF 中的 TAL 中的 cAMP 形成有影响。
