The Combination of ACE Inhibition plus Sympathetic Denervation Is Superior to ACE Inhibitor Monotherapy in the Rat Renal Ablation Model

BACKGROUND: The blood pressure-independent renoprotective actions of the blockade of the renin-angiotensin and the sympathetic nervous system are well documented, but monotherapies fail to completely abrogate progression. We investigated whether combined inhibition of the two systems provides additive renoprotection. METHODS: After subtotal nephrectomy (SNX) or sham operation, rats underwent resection of dorsal roots, i.e. rhizotomy or sham rhizotomy. Subsequently, they received tap water or quinapril in drinking water for 16 weeks (n = 18/group). Albuminuria, blood pressure and kidneys were assessed (morphometry, immunohistochemistry). RESULTS: At the end of the study telemetric blood pressure in SNX was 118 +/- 16 mm Hg, in SNX + rhizotomy 110 +/- 10 mm Hg, in SNX + quinapril 103 +/- 9 mm Hg and in SNX + quinapril + rhizotomy 95 +/- 7 mm Hg. Albuminuria in the respective groups was 169 +/- 75, 86 +/- 45, 15 +/- 23 and 5 +/- 4 mg/24 h. The glomerulosclerosis index was 1.40 +/- 0.6, 0.80 +/- 0.23, 0.37 +/- 0.16 and 0.31 +/- 0.15 (p < 0.001). Only combined intervention caused significant reduction of the glomerular volume and podocyte hypertrophy. The lowest indices for nitrotyrosine, NOS-1 (nNOS), TGF-beta and interstitial collagen were seen with combined interventions (p < 0.05). CONCLUSION: In angiotensin-converting enzyme inhibitor-treated SNX animals, abrogation of sympathetic overactivity provides additional renoprotection and less nitro-oxidative stress of podocytes than single interventions. The added benefits were partially blood pressure independent.