Abstract
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.
Highlights
During pregnancy, the uterus undergoes significant and expansive hypertrophy and distension to provide the adequate space for the growing fetus, while placental remodeling and cytotrophoblast invasion of spiral arteries occur to supply blood flow required for the fetal developing [1,2]
Increases in systolic blood pressure occurred after one day of L-NAME injections when compared to day one in Virgin group (*P < 0.05), and systolic blood pressure was maintained elevated in Virgin+L-NAME compared to respective days in Virgin group (*,# P < 0.05, Figure 1A)
In order to expand the knowledge of mmPs activity regulation in vivo and during pregnancy compared to non-pregnancy conditions, we examined whether nitric oxide (NO) bioavailability could have an association with changes in the activity of mmPs during normotensive and hypertensive pregnancy compared to virgin rats
Summary
The uterus undergoes significant and expansive hypertrophy and distension to provide the adequate space for the growing fetus, while placental remodeling and cytotrophoblast invasion of spiral arteries occur to supply blood flow required for the fetal developing [1,2]. Hemodynamic changes as increases in maternal blood volume and cardiac output are counterbalanced by systemic vasodilation following decreases in vascular resistance occur during the gestational period [3,4]. These utero-placental and vascular changes may be modulated by nitric oxide (NO) [5,6]. The gelatinases mmP-2 and mmP-9 have been implicated in these pregnancy-associated changes [8,9]. It is unclear whether the activity of mmP-2 and mmP-9 is regulated by endogenous NO during pregnancy.
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