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Antihypertensive effects of inducible nitric oxide synthase inhibition in experimental pre‐eclampsia
by
Palei, Ana C.T.
, Portella, Rafael L.
, Tanus‐Santos, Jose E.
, Pinheiro, Lucas C.
, Amaral, Lorena M.
, Guimaraes, Danielle A.
, Sertório, Jonas T.
in
Abdomen
/ Animal models
/ Animals
/ Antihypertensive Agents - therapeutic use
/ Antihypertensives
/ Aorta
/ Blood pressure
/ Chemiluminescence
/ Coronary vessels
/ Cytokines
/ Enzyme-linked immunosorbent assay
/ Female
/ Hypertension
/ Hypotheses
/ Immunohistochemistry
/ inducible nitric oxide synthase
/ Inflammation
/ Ischemia
/ Laboratory animals
/ Microscopy
/ NADP
/ NADPH-diaphorase
/ Nitric oxide
/ Nitric Oxide Synthase Type II - antagonists & inhibitors
/ Nitric-oxide synthase
/ Nitrotyrosine
/ Original
/ Oxidative stress
/ Pathogenesis
/ Perfusion
/ Placenta
/ Pre-Eclampsia - drug therapy
/ Pre-Eclampsia - enzymology
/ Preeclampsia
/ Pregnancy
/ Pre‐eclampsia
/ Rats
/ Reactive oxygen species
/ reduced uteroplacental perfusion pressure
/ Rodents
/ RUPP
/ Studies
/ Veins & arteries
/ Western blotting
2013
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Antihypertensive effects of inducible nitric oxide synthase inhibition in experimental pre‐eclampsia
by
Palei, Ana C.T.
, Portella, Rafael L.
, Tanus‐Santos, Jose E.
, Pinheiro, Lucas C.
, Amaral, Lorena M.
, Guimaraes, Danielle A.
, Sertório, Jonas T.
in
Abdomen
/ Animal models
/ Animals
/ Antihypertensive Agents - therapeutic use
/ Antihypertensives
/ Aorta
/ Blood pressure
/ Chemiluminescence
/ Coronary vessels
/ Cytokines
/ Enzyme-linked immunosorbent assay
/ Female
/ Hypertension
/ Hypotheses
/ Immunohistochemistry
/ inducible nitric oxide synthase
/ Inflammation
/ Ischemia
/ Laboratory animals
/ Microscopy
/ NADP
/ NADPH-diaphorase
/ Nitric oxide
/ Nitric Oxide Synthase Type II - antagonists & inhibitors
/ Nitric-oxide synthase
/ Nitrotyrosine
/ Original
/ Oxidative stress
/ Pathogenesis
/ Perfusion
/ Placenta
/ Pre-Eclampsia - drug therapy
/ Pre-Eclampsia - enzymology
/ Preeclampsia
/ Pregnancy
/ Pre‐eclampsia
/ Rats
/ Reactive oxygen species
/ reduced uteroplacental perfusion pressure
/ Rodents
/ RUPP
/ Studies
/ Veins & arteries
/ Western blotting
2013
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Antihypertensive effects of inducible nitric oxide synthase inhibition in experimental pre‐eclampsia
by
Palei, Ana C.T.
, Portella, Rafael L.
, Tanus‐Santos, Jose E.
, Pinheiro, Lucas C.
, Amaral, Lorena M.
, Guimaraes, Danielle A.
, Sertório, Jonas T.
in
Abdomen
/ Animal models
/ Animals
/ Antihypertensive Agents - therapeutic use
/ Antihypertensives
/ Aorta
/ Blood pressure
/ Chemiluminescence
/ Coronary vessels
/ Cytokines
/ Enzyme-linked immunosorbent assay
/ Female
/ Hypertension
/ Hypotheses
/ Immunohistochemistry
/ inducible nitric oxide synthase
/ Inflammation
/ Ischemia
/ Laboratory animals
/ Microscopy
/ NADP
/ NADPH-diaphorase
/ Nitric oxide
/ Nitric Oxide Synthase Type II - antagonists & inhibitors
/ Nitric-oxide synthase
/ Nitrotyrosine
/ Original
/ Oxidative stress
/ Pathogenesis
/ Perfusion
/ Placenta
/ Pre-Eclampsia - drug therapy
/ Pre-Eclampsia - enzymology
/ Preeclampsia
/ Pregnancy
/ Pre‐eclampsia
/ Rats
/ Reactive oxygen species
/ reduced uteroplacental perfusion pressure
/ Rodents
/ RUPP
/ Studies
/ Veins & arteries
/ Western blotting
2013
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Antihypertensive effects of inducible nitric oxide synthase inhibition in experimental pre‐eclampsia
Journal Article
Antihypertensive effects of inducible nitric oxide synthase inhibition in experimental pre‐eclampsia
2013
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Overview
Upregulation of inducible nitric oxide synthase (iNOS) has been reported in both experimental and clinical hypertension. However, although pro‐inflammatory cytokines that up‐regulate iNOS contribute to pre‐eclampsia, no previous study has tested the hypothesis that a selective iNOS inhibitor (1400 W) could exert antihypertensive effects associated with decreased iNOS expression and nitrosative stress in pre‐eclampsia. This study examined the effects of 1400 W in the reduced uteroplacental perfusion pressure (RUPP) placental ischaemia animal model and in normal pregnant rats. Sham‐operated and RUPP rats were treated with daily vehicle or 1 mg/kg/day N‐[3‐(Aminomethyl) benzyl] acetamidine (1400 W) subcutaneously for 5 days. Plasma 8‐isoprostane levels, aortic reactive oxygen species (ROS) levels and nicotinamide adenine dinucleotide phosphate (NADPH)‐dependent ROS production were evaluated by ELISA, dihydroethidium fluorescence microscopy and lucigenin chemiluminescence respectively. Inducible nitric oxide synthase expression was assessed by western blotting analysis and aortic nitrotyrosine was evaluated by immunohistochemistry. Mean arterial blood pressure increased by ~30 mmHg in RUPP rats, and 1400 W attenuated this increase by ~50% (P < 0.05). While RUPP increased plasma 8‐isoprostane levels, aortic ROS levels, and NADPH‐dependent ROS production (P < 0.05), treatment with 1400 W blunted these alterations (P < 0.05). Moreover, while RUPP increased iNOS expression and aortic nitrotyrosine levels (P < 0.05), treatment with 1400 W blunted these alterations (P < 0.05). These results clearly implicate iNOS in the hypertension associated with RUPP. Our findings may suggest that iNOS inhibitors could be clinically useful in the therapy of pre‐eclampsia, especially in particular groups of patients genetically more prone to express higher levels of iNOS. This issue deserves further confirmation.
Publisher
John Wiley & Sons, Inc,Blackwell Publishing Ltd
Subject
/ Animals
/ Antihypertensive Agents - therapeutic use
/ Aorta
/ Enzyme-linked immunosorbent assay
/ Female
/ inducible nitric oxide synthase
/ Ischemia
/ NADP
/ Nitric Oxide Synthase Type II - antagonists & inhibitors
/ Original
/ Placenta
/ Pre-Eclampsia - drug therapy
/ Rats
/ reduced uteroplacental perfusion pressure
/ Rodents
/ RUPP
/ Studies
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