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Open AccessArticle

Reductions of Circulating Nitric Oxide are Followed by Hypertension during Pregnancy and Increased Activity of Matrix Metalloproteinases-2 and -9 in Rats

1
Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University – UNESP, Botucatu, Sao Paulo 18.618-689, Brazil
2
Unit of Biotechnology, University of Ribeirao Preto, UNAERP, Ribeirao Preto, Sao Paulo 14096-900, Brazil
*
Author to whom correspondence should be addressed.
Cells 2019, 8(11), 1402; https://doi.org/10.3390/cells8111402
Received: 8 August 2019 / Accepted: 3 September 2019 / Published: 7 November 2019
(This article belongs to the Special Issue Extracellular Matrix Remodeling 2019)
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. View Full-Text
Keywords: hypertensive pregnancy; metalloproteinases; nitric oxide; rats hypertensive pregnancy; metalloproteinases; nitric oxide; rats
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Nascimento, R.A.; Possomato-Vieira, J.S.; Bonacio, G.F.; Rizzi, E.; Dias-Junior, C.A. Reductions of Circulating Nitric Oxide are Followed by Hypertension during Pregnancy and Increased Activity of Matrix Metalloproteinases-2 and -9 in Rats. Cells 2019, 8, 1402.

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