Hypertension, augmented activity of matrix metalloproteinases-2 and -9 and angiogenic imbalance in hypertensive pregnancy are attenuated by doxycycline
| Autor: | Gisele F. Bonacio, Jose Sergio Possomato-Vieira, Victor Hugo Gonçalves-Rizzi, Carlos A. Dias-Junior, Elen Rizzi, Regina Aparecida Nascimento |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), UNAERP |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Placental growth factor medicine.medical_specialty Litter Size Placenta Hypertension in Pregnancy Neovascularization Physiologic 030204 cardiovascular system & hematology Matrix metalloproteinase Nitric Oxide Antioxidants Nitric oxide Preeclampsia Hypertensive pregnancy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pregnancy Internal medicine medicine Animals Maternal hypertension Rats Wistar Pharmacology Doxycycline business.industry Uterus Hypertension Pregnancy-Induced Organ Size medicine.disease Metalloproteinases Rats 030104 developmental biology Endocrinology Blood pressure Matrix Metalloproteinase 9 chemistry Matrix Metalloproteinase 2 Female business medicine.drug |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2018.10.017 |
| Popis: | Made available in DSpace on 2019-10-06T16:01:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-12-05 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Preeclampsia is manifested as maternal hypertension and fetal growth restriction. Matrix metalloproteinases (MMPs) are involved in hypertension and doxycycline reduces blood pressure by inhibition of MMPs. Moreover, excessive levels of MMPs and reduced nitric oxide (NO) bioavailability have been related to preeclampsia. We investigated the involvement of MMPs in hypertension in pregnancy induced by Nω-Nitro-L-arginine methyl ester (L-NAME) in rats. To this end, zimography was performed to evaluate the activity of MMPs -2 and -9 in placenta, uterus and thoracic aorta, and systolic blood pressure, feto-placental development and metabolites of NO were evaluated. Also, plasma antioxidant capacity, plasma levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PLGF) were examined. Doxycycline prevented hypertensive pregnancy and significant reductions in number of pups induced by L-NAME. Low NO bioavailability was found in hypertensive pregnant rats treated (or not) with doxycycline. Increased activity of placental MMP-2 and MMP-9 and uterine MMP-2 were attenuated by doxycycline. MMP-2 activity of thoracic aorta showed no change after hypertension. Increases in PLGF with concomitant decreases in sFlt-1 levels were found with doxycycline treatment. Also, plasma antioxidant capacity was improved with doxycycline. Also, elevations of plasma antioxidant capacity were observed in hypertensive rats treated with doxycycline. Therefore, we suggest that L-NAME reduced NO and this triggered the increases in MMP-2 and -9 activities during hypertensive pregnancy. Importantly, increases in MMPs activation and angiogenic imbalance were attenuated by doxycycline and these effects were associated with decreases in systolic blood pressure. Department of Pharmacology Biosciences Institute of Botucatu Sao Paulo State University – UNESP Unit of Biotechnology University of Ribeirao Preto UNAERP Department of Pharmacology Biosciences Institute of Botucatu Sao Paulo State University – UNESP CAPES: 001 |
| Databáze: | OpenAIRE |
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