Effects of renal denervation on the NKCC2 cotransporter in the thick ascending limb of the loop of Henle in rats with congestive heart failure

Abstract

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.