Cargando…
Increased Cyclooxygenase-2-Derived Prostanoids Contributes to the Hyperreactivity to Noradrenaline in Mesenteric Resistance Arteries from Offspring of Diabetic Rats
This study analyzed the effect of in utero exposure to maternal diabetes on contraction to noradrenaline in mesenteric resistance arteries (MRA) from adult offspring, focusing on the role of cyclooxygenase (COX)-derived prostanoids. Diabetes in the maternal rat was induced by a single injection of s...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509067/ https://www.ncbi.nlm.nih.gov/pubmed/23209788 http://dx.doi.org/10.1371/journal.pone.0050593 |
_version_ | 1782251283389874176 |
---|---|
author | Ramos-Alves, Fernanda E. de Queiroz, Diego B. Santos-Rocha, Juliana Duarte, Gloria P. Xavier, Fabiano E. |
author_facet | Ramos-Alves, Fernanda E. de Queiroz, Diego B. Santos-Rocha, Juliana Duarte, Gloria P. Xavier, Fabiano E. |
author_sort | Ramos-Alves, Fernanda E. |
collection | PubMed |
description | This study analyzed the effect of in utero exposure to maternal diabetes on contraction to noradrenaline in mesenteric resistance arteries (MRA) from adult offspring, focusing on the role of cyclooxygenase (COX)-derived prostanoids. Diabetes in the maternal rat was induced by a single injection of streptozotocin (50 mg/kg body weight) on day 7 of pregnancy. Contraction to noradrenaline was analyzed in isolated MRA from offspring of diabetic (O-DR) and non-diabetic (O-CR) rats at 3, 6 and 12 months of age. Release of thromboxane A(2) (TxA(2)) and prostaglandins E(2) (PGE(2)) and F(2α) (PGF(2α)), was measured by specific enzyme immunoassay kits. O-DR developed hypertension from 6 months of age compared with O-CR. Arteries from O-DR were hyperactive to noradrenaline only at 6 and 12 months of age. Endothelial removal abolished this hyperreactivity to noradrenaline between O-CR and O-DR. Preincubation with either the COX-1/2 (indomethacin) or COX-2 inhibitor (NS-398) decreased noradrenaline contraction only in 6- and 12-month-old O-DR, while it remained unmodified by COX-1 inhibitor SC-560. In vessels from 6-month-old O-DR, a similar reduction in the contraction to noradrenaline produced by NS-398 was observed when TP and EP receptors were blocked (SQ29548+AH6809). In 12-month-old O-DR, this effect was only achieved when TP, EP and FP were blocked (SQ29548+AH6809+AL8810). Noradrenaline-stimulated TxB(2) and PGE(2) release was higher in 6- and 12-month-old O-DR, whereas PGF(2α) was increased only in 12-month-old O-DR. Our results demonstrated that in utero exposure to maternal hyperglycaemia in rats increases the participation of COX-2-derived prostanoids on contraction to noradrenaline, which might help to explain the greater response to this agonist in MRA from 6- and 12-month-old offspring. As increased contractile response in resistance vessels may contribute to hypertension, our results suggest a role for these COX-2-derived prostanoids in elevating vascular resistance and blood pressure in offspring of diabetic rats. |
format | Online Article Text |
id | pubmed-3509067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35090672012-12-03 Increased Cyclooxygenase-2-Derived Prostanoids Contributes to the Hyperreactivity to Noradrenaline in Mesenteric Resistance Arteries from Offspring of Diabetic Rats Ramos-Alves, Fernanda E. de Queiroz, Diego B. Santos-Rocha, Juliana Duarte, Gloria P. Xavier, Fabiano E. PLoS One Research Article This study analyzed the effect of in utero exposure to maternal diabetes on contraction to noradrenaline in mesenteric resistance arteries (MRA) from adult offspring, focusing on the role of cyclooxygenase (COX)-derived prostanoids. Diabetes in the maternal rat was induced by a single injection of streptozotocin (50 mg/kg body weight) on day 7 of pregnancy. Contraction to noradrenaline was analyzed in isolated MRA from offspring of diabetic (O-DR) and non-diabetic (O-CR) rats at 3, 6 and 12 months of age. Release of thromboxane A(2) (TxA(2)) and prostaglandins E(2) (PGE(2)) and F(2α) (PGF(2α)), was measured by specific enzyme immunoassay kits. O-DR developed hypertension from 6 months of age compared with O-CR. Arteries from O-DR were hyperactive to noradrenaline only at 6 and 12 months of age. Endothelial removal abolished this hyperreactivity to noradrenaline between O-CR and O-DR. Preincubation with either the COX-1/2 (indomethacin) or COX-2 inhibitor (NS-398) decreased noradrenaline contraction only in 6- and 12-month-old O-DR, while it remained unmodified by COX-1 inhibitor SC-560. In vessels from 6-month-old O-DR, a similar reduction in the contraction to noradrenaline produced by NS-398 was observed when TP and EP receptors were blocked (SQ29548+AH6809). In 12-month-old O-DR, this effect was only achieved when TP, EP and FP were blocked (SQ29548+AH6809+AL8810). Noradrenaline-stimulated TxB(2) and PGE(2) release was higher in 6- and 12-month-old O-DR, whereas PGF(2α) was increased only in 12-month-old O-DR. Our results demonstrated that in utero exposure to maternal hyperglycaemia in rats increases the participation of COX-2-derived prostanoids on contraction to noradrenaline, which might help to explain the greater response to this agonist in MRA from 6- and 12-month-old offspring. As increased contractile response in resistance vessels may contribute to hypertension, our results suggest a role for these COX-2-derived prostanoids in elevating vascular resistance and blood pressure in offspring of diabetic rats. Public Library of Science 2012-11-28 /pmc/articles/PMC3509067/ /pubmed/23209788 http://dx.doi.org/10.1371/journal.pone.0050593 Text en © 2012 Ramos-Alves et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ramos-Alves, Fernanda E. de Queiroz, Diego B. Santos-Rocha, Juliana Duarte, Gloria P. Xavier, Fabiano E. Increased Cyclooxygenase-2-Derived Prostanoids Contributes to the Hyperreactivity to Noradrenaline in Mesenteric Resistance Arteries from Offspring of Diabetic Rats |
title | Increased Cyclooxygenase-2-Derived Prostanoids Contributes to the Hyperreactivity to Noradrenaline in Mesenteric Resistance Arteries from Offspring of Diabetic Rats |
title_full | Increased Cyclooxygenase-2-Derived Prostanoids Contributes to the Hyperreactivity to Noradrenaline in Mesenteric Resistance Arteries from Offspring of Diabetic Rats |
title_fullStr | Increased Cyclooxygenase-2-Derived Prostanoids Contributes to the Hyperreactivity to Noradrenaline in Mesenteric Resistance Arteries from Offspring of Diabetic Rats |
title_full_unstemmed | Increased Cyclooxygenase-2-Derived Prostanoids Contributes to the Hyperreactivity to Noradrenaline in Mesenteric Resistance Arteries from Offspring of Diabetic Rats |
title_short | Increased Cyclooxygenase-2-Derived Prostanoids Contributes to the Hyperreactivity to Noradrenaline in Mesenteric Resistance Arteries from Offspring of Diabetic Rats |
title_sort | increased cyclooxygenase-2-derived prostanoids contributes to the hyperreactivity to noradrenaline in mesenteric resistance arteries from offspring of diabetic rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509067/ https://www.ncbi.nlm.nih.gov/pubmed/23209788 http://dx.doi.org/10.1371/journal.pone.0050593 |
work_keys_str_mv | AT ramosalvesfernandae increasedcyclooxygenase2derivedprostanoidscontributestothehyperreactivitytonoradrenalineinmesentericresistancearteriesfromoffspringofdiabeticrats AT dequeirozdiegob increasedcyclooxygenase2derivedprostanoidscontributestothehyperreactivitytonoradrenalineinmesentericresistancearteriesfromoffspringofdiabeticrats AT santosrochajuliana increasedcyclooxygenase2derivedprostanoidscontributestothehyperreactivitytonoradrenalineinmesentericresistancearteriesfromoffspringofdiabeticrats AT duartegloriap increasedcyclooxygenase2derivedprostanoidscontributestothehyperreactivitytonoradrenalineinmesentericresistancearteriesfromoffspringofdiabeticrats AT xavierfabianoe increasedcyclooxygenase2derivedprostanoidscontributestothehyperreactivitytonoradrenalineinmesentericresistancearteriesfromoffspringofdiabeticrats |