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

Abstract

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-β 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.

Renoprotective effects of telmisartan in the 5/6 nephrectomised rats

“…37 In subtotally nephrectomised rats podocyte damage by nitrooxidative stress was attenuated by sympathetic denervation as well as ACE-inhibition. 38 In the present study, podoplanin expression was decreased in the vehicle group, while the decrease in podoplanin expression was suppressed in the telmisartan group at all doses tested (figure 4). These findings show that it is possible to attenuate renal damage in 5/6 Nx rats by the non-haemodynamic actions (e.g.…”

Heart Rate Variability Predicts ESRD and CKD-Related Hospitalization

“…48 Some of the renoprotective effects of these agents may be mediated in part by cross-talk between the sympathetic nervous system and the renin-angiotensin-aldosterone system. 49 Although animal models indicate that sympathetic denervation of the kidneys can provide renoprotective effects, 50 there is little evidence that centrally or peripherally acting sympatholytics have unique renoprotective effects in humans. 51 Rather than suggesting a change in clinical practice, we hope our findings will encourage further research to better define the putative role of the autonomic nervous system in precipitating and exacerbating renal disease in humans; this, in turn, may ultimately lead to novel therapeutic approaches once the mechanisms for our findings are better characterized.…”

Cardiovascular Problems on Hemodialysis

“…The adverse effect of catecholamine excess on cardiac function is widely known, and a strong case can be made for the use of ␤ blockers in renal patients (45). In models of impaired renal function, ␤ receptor blockade attenuates progression even when given on top of renin-angiotensin system blockade (46). In experimental studies, ␤ blockade affects cardiac function and ameliorates even one facet of uremic cardiomyopathy: the capillary deficit (47).…”