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Kidney Week

Abstract: SA-PO396

Sex Differences in the Exacerbating Effects of Chronic Nicotine on Angiotensin II-Induced Renal Injury

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Maranon, Rodrigo, University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Chandrashekar, Kiran B., UMMC , Brandon, Mississippi, United States
  • Juncos, Luis A., University of Mississippi Medical Center, Jackson, Mississippi, United States
Background

Chronic Nicotine (Ch-Nic) worsens angiotensin II (AngII)-induced renal injury in male rodents via various mechanisms that alter heme oxygenase and oxidant stress. Because females may regulate these factors differently, and also metabolize nicotine than males, we tested whether Ch-Nic exacerbates AngII-induced renal injury in females to the same extent as in males. For this, we tested male and female Sprague Dawley rats for 60 days with Ch-Nic (12.5µg/ml) or vehicle in water, and then randomized into 4 groups each, which received either AngII (200ng/kg/min) or vehicle via SQ osmotic minipumps for an additional 28 days. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography twice weekly and parameters of renal function and injury were assessed at the end of the experiments.

See Table below.

Conclusion

Cotinine excretion rates were 5 times higher in females than males, suggesting that females metabolize nicotine much faster and thus may be protected against the deleterious effects of Ch-Nic. Despite this, Ch-Nic exacerbated AngII-induced renal injury in both males and females, albeit with some differences. Males developed proteinuria earlier than females, and sustained higher levels of proteinuria throughout the study. Despite less proteinuria, NGAl and inflammation (TNF), females appeared to lose more GFR, as suggested by the more pronounced increase in serum creatinine levels. Our data indicate that despite the rapid metabolism of nicotine in females, Ch-Nic still induces renal injury in them. The differences in the pattern of injury and lack of inflammation, raise the possibility that the mechanisms of renal injury are different between the sexes.

Funding

  • NIDDK Support