Why the study?
Hypertensive pregnancy is linked to reduced nitric oxide bioavailability and increased matrix metalloproteinase activity, but whether nitric oxide regulates matrix metalloproteinase activation during pregnancy remains unclear.
Does L-NAME-induced reduction in NO bioavailability increase MMP activity and cause hypertension in pregnant rats?
Does L-NAME-induced reduction in NO bioavailability increase MMP activity and cause hypertension in pregnant rats?
Reduced nitric oxide bioavailability may drive the activation of matrix metalloproteinases and contribute to hypertension and fetal growth restriction during pregnancy.
L-NAME rat model links reduced NO to MMP activation and gestational hypertension; leaves open translation to human preeclampsia.
Hypertensive pregnancy has been associated with reduced nitric oxide (NO), bioavailability, and increased activity of matrix metalloproteinases (MMPs). However, it is unclear if MMPs activation is regulated by NO during pregnancy. To this end, we examined activity of MMP-2 and MMP-9 in plasma, placenta, uterus and aorta, NO bioavailability, oxidative stress, systolic blood pressure (SBP), and fetal-placental development at the early, middle, and late pregnancy stages in normotensive and Nω-Nitro-L-arginine methyl-ester (L-NAME)-induced hypertensive pregnancy in rats. Reduced MMP-2 activity in uterus, placenta, and aorta and reduced MMP-9 activity in plasma and placenta with concomitant increased NO levels were found in normotensive pregnant rats. By contrast, increased MMP-2 activity in uterus, placenta, and aorta, and increased MMP-9 activity in plasma and placenta with concomitant reduced NO levels were observed in hypertensive pregnant rats. Also, elevated oxidative stress was displayed by hypertensive pregnant rats at the middle and late stages. These findings in the L-NAME-treated pregnant rats were also followed by increases in SBP and associated with fetal growth restrictions at the middle and late pregnancy stages. We concluded that NO bioavailability may regulate MMPs activation during normal and hypertensive pregnancy.
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Nascimento et al. (2019) studied this question.
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