Cigarette exposure induces changes in maternal vascular function in a pregnant mouse model

Abstract

Smoking is associated with multiple adverse pregnancy outcomes, including fetal growth restriction. The objective of this study was to determine whether cigarette smoke exposure during pregnancy in a mouse model affects the functional properties of maternal uterine, mesenteric, and renal arteries as a possible mechanism for growth restriction. C57Bl/CJ mice were exposed to whole body sidestream smoke for 4 h/day. Smoke particle exposure was increased from day 4 of gestation until late pregnancy (day 16-19), with mean total suspended particle levels of 63 mg/m(3), representative of moderate-to-heavy smoking in humans. Uterine, mesenteric, and renal arteries from late-pregnant and virgin mice were isolated and studied in a pressure-arteriograph system (n = 23). Plasma cotinine was measured by ELISA. Fetal weights were significantly reduced in smoke-exposed compared with control fetuses (0.88 +/- 0.1 vs. 1.0 +/- 0.08 g, P < 0.02), while litter sizes were not different. Endothelium-mediated relaxation responses to methacholine were significantly impaired in both the uterine and mesenteric vasculature of pregnant mice exposed to cigarette smoke during gestation. This difference was not apparent in isolated renal arteries from pregnant mice exposed to cigarette smoke; however, relaxation was significantly reduced in renal arteries from smoke-exposed virgin mice. In conclusion, we found that passive cigarette smoke exposure is associated with impaired vascular relaxation of uterine and mesenteric arteries in pregnant mice. Functional maternal vascular perturbations during pregnancy, specifically impaired peripheral and uterine vasodilation, may contribute to a mechanism by which smoking results in fetal growth restriction.

Fig. 1.

Endothelium-mediated relaxation responses to methacholine in arteries isolated from pregnant (A–C) and virgin (D–F) mice. Relaxation responses were impaired in uterine (A) and mesenteric (B) arteries from smoke-exposed pregnant mice but not in uterine (D) and mesenteric (E) arteries from virgin mice. In renal arteries (C and F), relaxation was significantly reduced only in smoke-exposed virgin mice (F). +P ≤ 0.05 (by 2-way repeated-measures ANOVA).

Fig. 2.

Myogenic reactivity assessed in isolated arterial segments using repeated steps in pressure from 60 to 80 mmHg. Myogenic reactivity of uterine (A) or mesenteric (B) arteries was not significantly different between control and smoke-exposed mice. Myogenic reactivity was significantly less in renal arteries from control pregnant mice (C) than in renal arteries from either smoke-exposed pregnant or virgin mice. Myogenic reactivity in renal arteries was significantly less (P < 0.05) in control pregnant mice than in control virgin (+) and smoke-exposed pregnant (*) mice (by 1-way ANOVA).

Fig. 3.

Distensibility curves of isolated uterine arteries (A) and stress-strain characteristics (B) of isolated uterine arteries from control virgin (CV), control pregnant (CP), smoke-exposed virgin (SV), and smoke-exposed pregnant (SP) mice. *P ≤ 0.040, CP vs. SV; +P ≤ 0.018, CP vs. CV; −P ≤ 0.030, SP vs. SV; ^P ≤ 0.011, CP vs. SP (by 2-way repeated-measures ANOVA).