Abstract: SA-PO398

Chronic Nicotine Mediated Accentuation of Angiotensin-II-Induced Renal Injury Is Prevented but Not Readily Reversed by Sildenafil

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Chandrashekar, Kiran B., UMMC , Brandon, Mississippi, United States
  • Maranon, Rodrigo, University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Lopez-Ruiz, Arnaldo F., None, Rochester, Minnesota, United States
  • Arany, Istvan, Dept. Pediatrics, Dv. Pediatric Nephrology, UMC, Jackson, Mississippi, United States
  • Juncos, Luis A., University of Mississippi Medical Center, Jackson, Mississippi, United States
Background

Chronic Nicotine (Ch-Nic) exacerbates angiotensin II (AngII)-induced renal dysfunction. Because sildenafil can preserve cGMP levels and increase heme oxygenase 1, both of which are protective against renal injury, we tested whether early administration of sildenafil prevents Ch-Nic-mediated exacerbation of AngII-induced renal injury. We also tested whether late administration sildenafil, after there is established renal injury, halts or reverses the progression of renal dysfunction

Methods

Sprague Dawley rats received nicotine (12 g/ml in their drinking water) with or without SP-AngII (200ng/kg/min via SQ infusion for 22 days). Separate groups were also concomitantly treated with sildenafil from either day 0 (Early sildenafil) or day 14 (Late sildenafil). Systolic blood pressure (SBP) was measured throughout and renal vascular resistance (OM-RVR) calculated. Renal function (plasma creatinine), pro-inflammatory (TNF-alfa), renal injury (NGAL), pro-apoptotic (cyt-c) and pro-fibrotic (TGF-beta) markers were assessed by ELISA. HO activity was evaluated based on the amount of bilirubin generated.

Results

p≤ 0.05: * vs. Control; # vs. Ang-II; Ω vs. AngII+ NIC. Early sildenafil treatment was very effective at decreasing Ch-Nic mediated exacerbation of AngII-induced renal dysfunction, inflammation, injury, and pro-apoptotic and pro-fibrotic signaling while increasing HO activity. In contrast, late sildenafil decreased blood pressure, but was much less effective at improving renal parameters of injury

Conclusion

Our data indicates early SIL therapy may ameliorate the exacerbating effects of NIC in a SP-AngII hypertensive model,but longer term studies are necessary to determine whether it can prevent progression or cause reversal of injury.

Funding

  • NIDDK Support