Effects of caffeine on placental total nitrite concentration: A 21-day, vehicle-controlled study in rats

Nitric oxide (NO) is a potent vasodilator that might have an10 important role in the modulation of maternal and fetal vascular tone during pregnancy. The effects of caffeine intake on maternal and fetal hemodynamic properties during pregnancy have been investigated in several human and animal studies. However, based on a literature search, there has been no study of placental total nitrite (a stable product of NO) concentration (PTNC) in pregnant humans or rats given caffeine.

The aim of this study was to assess the effects of caffeine intake 10 on PTNC in rats.

This 21-day, vehicle-controlled study was conducted at the Department10 of Pharmacology, Gaziantep University Hospital, Gaziantep, Turkey. Female Wistar rats were randomly assigned; based on age and weight, to receive 25, 50, or 100 mg/kg QD caffeine or 50 mg/kg QD isotonic saline solution (vehicle; age-matched control group), intraperitoneally for 21 days. After euthanization of the rats and cesarean section, the numbers of fetuses and fetal deaths were counted. The lengths and weights of the fetuses in each study group were noted. PTNC in the rats was determined using the Greiss reaction.

This study included 26 rats (7, 7, and 6 rats in the groups receiving10 25, 50, and 100 mg/kg. d caffeine, respectively; 6 rats in the control group). The mean (SD) lengths of the fetuses of the rats given 25, 50, and 100 mg/kg · d caffeine (4.90 [0.15], 4.02 [0.27], and 3.45 [0.17] mm, respectively) were significantly less compared with controls (5.10 [0.18] mm) (all, P < 0.001), as were the mean (SD) weights of the fetuses of rats given caffeine (5.86 [0.24], 4.97 [0.59], and 3.41 [0.23] g, respectively) versus controls (6.18 [0.21] g) (all, P < 0.001). The mean (SD) PTNCs in rats given 25, 50, and 100 mg/kg. d caffeine (19.82 [1.97], 29.39 [2.07], and 45.51 [7.66] nmol/g, respectively) were significantly higher compared with controls (16.10 [2.12] nmol/g) (all, P < 0.001).

The results of this study in rats suggest that caffeine intake 10 might increase NO production in the placenta. In addition, based on our findings and those from previous studies, we suggest that this increase might be an adaptive physiologic response to prevent undesirable effects of caffeine on vascular tone during pregnancy.