title: 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.
authors.affiliation: Renal Division, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Vanessa Meira
authors.initials: VM
authors.lastname: Ferreira
authors.affiliation: Renal Division, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Clevia Santos
authors.initials: CS
authors.lastname: Passos
authors.affiliation: Renal Division, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Edgar
authors.initials: E
authors.lastname: Maquigussa
authors.affiliation: Cardiovascular Division, Department of Physiology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Roberto Braz
authors.initials: RB
authors.lastname: Pontes
authors.affiliation: Cardiovascular Division, Department of Physiology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Cassia Toledo
authors.initials: CT
authors.lastname: Bergamaschi
authors.affiliation: Cardiovascular Division, Department of Physiology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Ruy Ribeiro
authors.initials: RR
authors.lastname: Campos
authors.affiliation: Renal Division, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Mirian Aparecida
authors.initials: MA
authors.lastname: Boim
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007668:Kidney / Q000503:physiopathology; D009538:Nicotine / Q000009:adverse effects*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis; D018000:Receptors, Peptide / Q000096:biosynthesis; D012065:Relaxin / Q000378:metabolism; D017595:Renal Plasma Flow / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C504789:Rxfp1 protein, rat; D009569:Nitric Oxide; D009538:Nicotine; D012065:Relaxin; D052247:Nitric Oxide Synthase Type II