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. 2024 Oct 15;25(20):11051.
doi: 10.3390/ijms252011051.

Impaired Endothelium-Dependent Vasodilation and Increased Levels of Soluble Fms-like Tyrosine Kinase-1 Induced by Reduced Uterine Perfusion Pressure in Pregnant Rats: Evidence of Protective Effects with Sodium Nitrite Treatment in Preeclampsia

Maria Luiza Santos Da Silva  1 , Sáskia Estela Biasotti Gomes  1 , Laisla Zanetoni Martins  1 , Serginara David Rodrigues  1 , Cristal de Jesus Toghi  1 , Carlos Alan Dias-Junior  1
Affiliations

Impaired Endothelium-Dependent Vasodilation and Increased Levels of Soluble Fms-like Tyrosine Kinase-1 Induced by Reduced Uterine Perfusion Pressure in Pregnant Rats: Evidence of Protective Effects with Sodium Nitrite Treatment in Preeclampsia

Maria Luiza Santos Da Silva et al. Int J Mol Sci. .

Abstract

Preeclampsia (PE) is a hypertensive disorder of pregnancy and is associated with increases in soluble fms-like tyrosine kinase-1 (sFlt-1) and reductions in nitric oxide (NO) levels. Placental ischemia and hypoxia are hypothesized as initial pathophysiological events of PE. Nitrite (NO metabolite) may be recycled back to NO in ischemic and hypoxic tissues. Therefore, this study examined the sodium nitrite effects in an experimental model of PE. Pregnant rats received saline (Preg group) or sodium nitrite (Preg + Na-Nitrite group). Pregnant rats submitted to the placental ischemia received saline (RUPP group) or sodium nitrite (RUPP + Na-Nitrite group). Blood pressure, placental and fetal weights, and the number of pups were recorded. Plasma levels of NO metabolites and sFlt-1 were also determined. Vascular and endothelial functions were also measured. Blood pressure, placental and fetal weights, the number of pups, NO metabolites, sFlt-1 levels, vascular contraction, and endothelium-dependent vasodilation in the RUPP + Na-Nitrite rats were brought to levels comparable to those in Preg rats. In conclusion, sodium nitrite may counteract the reductions in NO and increases in sFlt-1 levels induced by the placental ischemia model of PE, thus suggesting that increased blood pressure and vascular and endothelial dysfunctions may be attenuated by sodium nitrite-derived NO.

Keywords: endothelial dysfunction; nitric oxide; placental ischemia; preeclampsia; sodium nitrite.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Effects of sodium nitrite on systolic blood pressure (SBP) measured on pregnancy day 21 in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (n = 8–10 animals per group). Values represent the mean ± SEM. & p < 0.05 vs. the Preg, RUPP, and RUPP+Na-Nitrite groups; * p < 0.05 vs. the Preg group; # p < 0.05 vs. the RUPP group.
Figure 2
Figure 2
Effects of sodium nitrite on placental weight recorded in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (n = 8–10 mothers per group). Values represent the mean ± SEM. & p < 0.05 vs. the Preg and RUPP groups; * p < 0.05 vs. the Preg group; # p < 0.05 vs. the RUPP group.
Figure 3
Figure 3
Effects of sodium nitrite on fetal weight recorded in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (n = 8–10 mothers per group). Values represent the mean ± SEM. * p < 0.05 vs. the Preg group; & p < 0.05 vs. the Preg and Preg+Na-Nitrite groups; # p < 0.05 vs. the RUPP group.
Figure 4
Figure 4
Effects of sodium nitrite on litter size (total number of pups) noted in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (n = 8–10 mothers per group). Values represent the mean ± SEM. * p < 0.05 vs. the Preg group; & p < 0.05 vs. the Preg and Preg+Na-Nitrite groups; # p < 0.05 vs. the RUPP group.
Figure 5
Figure 5
Effects of sodium nitrite on plasmatic NO metabolites (nitrite+nitrate levels) in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (n = 8–10 animals per group). Values represent the mean ± SEM. * p < 0.05 vs. the Preg group; & p < 0.05 vs. the Preg and Preg+Na-Nitrite groups; # p < 0.05 vs. the RUPP group.
Figure 6
Figure 6
Effects of sodium nitrite on circulating sFlt-1 levels in plasma from the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (n = 8–10 animals per group). Values represent the mean ± SEM. * p < 0.05 vs. the Preg, Preg+Na-Nitrite, and RUPP+Na-Nitrite groups.
Figure 7
Figure 7
Effects of sodium nitrite on the vascular reactivity of the thoracic aorta rings in the contraction induced by phenylephrine with (n = 2 rings per animal, (A)) or without (n = 2 rings per animal, (B)) endothelium in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (n = 8–10 animals per group). Values represent the mean ± SEM. * p < 0.05 vs. the Preg, Preg+Na-Nitrite, and RUPP+Na-Nitrite groups; # p < 0.05 for the RUPP and RUPP+Na-Nitrite vs. the Preg and Preg+Na-Nitrite groups.
Figure 8
Figure 8
Effects of sodium nitrite on the vascular reactivity of acetylcholine-induced relaxations in the endothelium-intact thoracic aortas (n = 2 rings per animal, (A)) or endothelium-denuded thoracic aortas (n = 2 rings per animal, (B)) or endothelium intact thoracic aortas pre-incubated with L-NAME (n = 2 rings per animal, (C)) in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (n = 8–10 animals per group). Values represent the mean ± SEM. * p < 0.05 vs. the Preg, Preg+Na-Nitrite, and RUPP+Na-Nitrite groups; # p < 0.05 vs. the Preg group.
Figure 9
Figure 9
Effects of sodium nitrite on the vascular reactivity of sodium nitroprusside-induced relaxations in the endothelium-intact thoracic aortas (n = 2 rings per animal, (A)) or endothelium-denuded thoracic aortas (n = 2 rings per animal, (B)) from the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (n = 8–10 animals per group). Values represent the mean ± SEM.
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