Ferreira Vanessa Meira, Passos Clevia Santos, Maquigussa Edgar, Pontes Roberto Braz, Bergamaschi Cassia Toledo, Campos Ruy Ribeiro, Boim Mirian Aparecida
Renal Division, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
Cardiovascular Division, Department of Physiology, Federal University of São Paulo, São Paulo, Brazil.
PLoS One. 2016 Feb 25;11(2):e0150096. doi: 10.1371/journal.pone.0150096. eCollection 2016.
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.
妊娠的特征是母体全身和肾内血管舒张，导致肾血浆流量（RPF）和肾小球滤过率（GFR）增加。这些反应主要由一氧化氮（NO）和松弛素介导。吸烟对母体妊娠适应性的影响尚不清楚。在此，我们评估了长期暴露于尼古丁对未孕（V）和妊娠14天（P）的Wistar大鼠全身和肾内参数的影响。V组和P组分别通过渗透微型泵接受生理盐水或尼古丁（6 mg·kg⁻¹·天⁻¹），持续28天，从诱导妊娠前14天开始。尼古丁使V组血压升高10%，并使妊娠引起的特征性低血压最小化。尼古丁主要在P组损害肾交感神经活动（rSNA）和压力反射敏感性，表明尼古丁对血压的影响不是由神经系统刺激介导的。尼古丁对V组大鼠的GFR没有影响，但使P组的GFR降低了30%。尼古丁下调了钠和水转运蛋白的肾表达，主要在P组导致钠排泄分数增加，表明尼古丁损害了正常妊娠所需的钠和水潴留。肾组织和肾动脉中诱导型一氧化氮合酶（iNOS）的表达以及松弛素受体（LGR7）的表达均降低。这些结果清楚地表明，尼古丁在未孕和妊娠动物中均诱导了有害影响，并消除了母体适应妊娠的能力。
