Chronic Nicotine Exposure Abolishes Maternal Systemic and Renal Adaptations to Pregnancy in Rats

Abstract

Pregnancy is characterized by maternal systemic and intrarenal vasodilation, leading to increases in the renal plasma flow (RPF) and glomerular filtration rate (GFR). These responses are mainly mediated by nitric oxide (NO) and relaxin. The impact of cigarette smoking on the maternal adaptations to pregnancy is unclear. Here we evaluated the effects of chronic exposure to nicotine on systemic and intrarenal parameters in virgin (V) and 14-day pregnant (P) Wistar rats. V and P groups received saline or nicotine (6 mg·kg-1·day-1) respectively, via osmotic minipumps for 28 days, starting 14 days before pregnancy induction. Nicotine induced a 10% increase in blood pressure in the V group and minimized the characteristic pregnancy-induced hypotension. Renal sympathetic nerve activity (rSNA) and baroreflex sensitivity were impaired by nicotine mainly in the P group, indicating that the effect of nicotine on blood pressure was not mediated by nervous system stimulation. Nicotine had no effect on GFR in the V rats but reduced GFR of the P group by 30%. Renal expression of sodium and water transporters was downregulated by nicotine, resulting in increased fractional sodium excretion mainly in the P group, suggesting that nicotine compromised the sodium and water retention required for normal gestation. There was a reduction in the expression of inducible NO synthase (iNOS) in both the kidney tissue and renal artery, as well as in the expression of the relaxin receptor (LGR7). These results clearly show that nicotine induced deleterious effects in both virgin and pregnant animals, and abolished the maternal capacity to adapt to pregnancy.

Effect of nicotine on placental ischemia-induced complement activation and hypertension in the rat

“…When one considers ischemia in the placenta and hypertension as the endpoint, the effects of nicotine are more difficult to determine since nicotine itself impacts blood pressure and may acutely contribute to constriction of arteries. Evidence suggests that chronic nicotine treatment expedites the onset of hypertension in genetically pre-disposed rats and high doses (6 mg nicotine/kg/day) blunt maternal systemic and renal adaptation to pregnancy (Ferreira et al 2016). Nicotine has also been implicated in the development of hypertension by affecting macrophage infiltration into the kidney (Harwani et al 2016).…”