Effect of preventive and regressive isosorbide 5-mononitrate treatment on catecholamine levels in plasma, platelets, adrenals, left ventricle and aorta in cyclosporin A-induced hypertensive rats
Autor(a) principal: | |
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Data de Publicação: | 2005 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/4758 https://doi.org/10.1016/j.lfs.2005.01.032 |
Resumo: | Increased vascular reactivity associated with cyclosporin A (CsA)-induced arterial hypertension might result from increased vasoconstriction and/or decreased vasodilatation. The administration of organic NO donors could have beneficial effects by the NO-cGMP reposition, but there is the risk of sympathetic nervous system worsening by neuro-hormonal counter-regulation. We evaluate the effect of preventive and regressive (curative) isosorbide 5-mononitrate (Is-5-Mn) treatment on blood pressures and on plasma, platelets, adrenals, left ventricle and aorta norepinephrine (NE) and epinephrine (E) contents, assessed by HPLC, in CsA-induced hypertensive rats. Five rat groups were tested: control (orange juice), CsA (5 mg/kg/day) and Is-5-Mn (150 mg/kg/day, bid) groups were treated for 7 weeks; preventive group (Is-5-Mn + CsA): Is-5-Mn during 2 weeks plus 7 weeks of Is-5-Mn + CsA; regressive group (CsA + Is-5-Mn): CsA during 7 weeks plus 5 weeks of CsA + Is-5-Mn. The increased BP in the CsA group was prevented, but was not reverted, by concomitant Is-5-Mn treatment. In the CsA-treated rats, there was a noticeable decrease in left ventricle NE and E contents and aorta NE levels and a moderate increase in circulating catecholamines, without significant effect in the adrenals values. When Is-5-Mn was preventively used, the CsA-induced effect on left ventricle and aorta was prevented. Concomitantly, however, the plasma-platelet catecholamine balance was disrupted, accumulating NE in plasma, whereas E increased in aorta, mimic the single Is-5-Mn-treated group. In opposition, in the group used as regressive Is-5-Mn therapy, the adrenals contents were higher compared with the CsA-group and, simultaneously, the CsA-evoked effects on circulating, left ventricle and aorta catecholamines were not reverted. In conclusion, regressive Is-5-Mn therapy was unable to attenuate CsA-induced catecholamine changes and BP values even worsened. On the contrary, preventive Is-5-Mn treatment prevented the catecholamine changes on left ventricle and aorta, but increased plasma NE and aorta E accumulation. Even though with those effects, hypertension development was totally prevented, suggesting that peripheral SNS per se cannot fully explain CsA-induced hypertension. Furthermore, Is-5-Mn might produce beneficial effects only if preventively employed but, considering the changes on peripheral catecholamine contents, a judicious evaluation of the nitrate therapy impact is recommended in order to avoid further deleterious effects. |
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Effect of preventive and regressive isosorbide 5-mononitrate treatment on catecholamine levels in plasma, platelets, adrenals, left ventricle and aorta in cyclosporin A-induced hypertensive ratsCyclosporin AArterial hypertensionIsosorbide 5-mononitrateNitric oxideCatecholaminesPlateletsPeripheral tissuesIncreased vascular reactivity associated with cyclosporin A (CsA)-induced arterial hypertension might result from increased vasoconstriction and/or decreased vasodilatation. The administration of organic NO donors could have beneficial effects by the NO-cGMP reposition, but there is the risk of sympathetic nervous system worsening by neuro-hormonal counter-regulation. We evaluate the effect of preventive and regressive (curative) isosorbide 5-mononitrate (Is-5-Mn) treatment on blood pressures and on plasma, platelets, adrenals, left ventricle and aorta norepinephrine (NE) and epinephrine (E) contents, assessed by HPLC, in CsA-induced hypertensive rats. Five rat groups were tested: control (orange juice), CsA (5 mg/kg/day) and Is-5-Mn (150 mg/kg/day, bid) groups were treated for 7 weeks; preventive group (Is-5-Mn + CsA): Is-5-Mn during 2 weeks plus 7 weeks of Is-5-Mn + CsA; regressive group (CsA + Is-5-Mn): CsA during 7 weeks plus 5 weeks of CsA + Is-5-Mn. The increased BP in the CsA group was prevented, but was not reverted, by concomitant Is-5-Mn treatment. In the CsA-treated rats, there was a noticeable decrease in left ventricle NE and E contents and aorta NE levels and a moderate increase in circulating catecholamines, without significant effect in the adrenals values. When Is-5-Mn was preventively used, the CsA-induced effect on left ventricle and aorta was prevented. Concomitantly, however, the plasma-platelet catecholamine balance was disrupted, accumulating NE in plasma, whereas E increased in aorta, mimic the single Is-5-Mn-treated group. In opposition, in the group used as regressive Is-5-Mn therapy, the adrenals contents were higher compared with the CsA-group and, simultaneously, the CsA-evoked effects on circulating, left ventricle and aorta catecholamines were not reverted. In conclusion, regressive Is-5-Mn therapy was unable to attenuate CsA-induced catecholamine changes and BP values even worsened. On the contrary, preventive Is-5-Mn treatment prevented the catecholamine changes on left ventricle and aorta, but increased plasma NE and aorta E accumulation. Even though with those effects, hypertension development was totally prevented, suggesting that peripheral SNS per se cannot fully explain CsA-induced hypertension. Furthermore, Is-5-Mn might produce beneficial effects only if preventively employed but, considering the changes on peripheral catecholamine contents, a judicious evaluation of the nitrate therapy impact is recommended in order to avoid further deleterious effects.http://www.sciencedirect.com/science/article/B6T99-4GCX1VG-4/1/d54115f2503e1738d366072f7506bb2e2005info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/4758http://hdl.handle.net/10316/4758https://doi.org/10.1016/j.lfs.2005.01.032engLife Sciences. 77:20 (2005) 2514-2528Reis, FlávioRocha, LuísPonte, LuísaAlcobia, TeresaAlmeida, LuísCosta-Almeida, CarlosTeixeira, Fredericoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2020-11-06T16:49:13Zoai:estudogeral.uc.pt:10316/4758Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:43:27.273885Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Effect of preventive and regressive isosorbide 5-mononitrate treatment on catecholamine levels in plasma, platelets, adrenals, left ventricle and aorta in cyclosporin A-induced hypertensive rats |
title |
Effect of preventive and regressive isosorbide 5-mononitrate treatment on catecholamine levels in plasma, platelets, adrenals, left ventricle and aorta in cyclosporin A-induced hypertensive rats |
spellingShingle |
Effect of preventive and regressive isosorbide 5-mononitrate treatment on catecholamine levels in plasma, platelets, adrenals, left ventricle and aorta in cyclosporin A-induced hypertensive rats Reis, Flávio Cyclosporin A Arterial hypertension Isosorbide 5-mononitrate Nitric oxide Catecholamines Platelets Peripheral tissues |
title_short |
Effect of preventive and regressive isosorbide 5-mononitrate treatment on catecholamine levels in plasma, platelets, adrenals, left ventricle and aorta in cyclosporin A-induced hypertensive rats |
title_full |
Effect of preventive and regressive isosorbide 5-mononitrate treatment on catecholamine levels in plasma, platelets, adrenals, left ventricle and aorta in cyclosporin A-induced hypertensive rats |
title_fullStr |
Effect of preventive and regressive isosorbide 5-mononitrate treatment on catecholamine levels in plasma, platelets, adrenals, left ventricle and aorta in cyclosporin A-induced hypertensive rats |
title_full_unstemmed |
Effect of preventive and regressive isosorbide 5-mononitrate treatment on catecholamine levels in plasma, platelets, adrenals, left ventricle and aorta in cyclosporin A-induced hypertensive rats |
title_sort |
Effect of preventive and regressive isosorbide 5-mononitrate treatment on catecholamine levels in plasma, platelets, adrenals, left ventricle and aorta in cyclosporin A-induced hypertensive rats |
author |
Reis, Flávio |
author_facet |
Reis, Flávio Rocha, Luís Ponte, Luísa Alcobia, Teresa Almeida, Luís Costa-Almeida, Carlos Teixeira, Frederico |
author_role |
author |
author2 |
Rocha, Luís Ponte, Luísa Alcobia, Teresa Almeida, Luís Costa-Almeida, Carlos Teixeira, Frederico |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Reis, Flávio Rocha, Luís Ponte, Luísa Alcobia, Teresa Almeida, Luís Costa-Almeida, Carlos Teixeira, Frederico |
dc.subject.por.fl_str_mv |
Cyclosporin A Arterial hypertension Isosorbide 5-mononitrate Nitric oxide Catecholamines Platelets Peripheral tissues |
topic |
Cyclosporin A Arterial hypertension Isosorbide 5-mononitrate Nitric oxide Catecholamines Platelets Peripheral tissues |
description |
Increased vascular reactivity associated with cyclosporin A (CsA)-induced arterial hypertension might result from increased vasoconstriction and/or decreased vasodilatation. The administration of organic NO donors could have beneficial effects by the NO-cGMP reposition, but there is the risk of sympathetic nervous system worsening by neuro-hormonal counter-regulation. We evaluate the effect of preventive and regressive (curative) isosorbide 5-mononitrate (Is-5-Mn) treatment on blood pressures and on plasma, platelets, adrenals, left ventricle and aorta norepinephrine (NE) and epinephrine (E) contents, assessed by HPLC, in CsA-induced hypertensive rats. Five rat groups were tested: control (orange juice), CsA (5 mg/kg/day) and Is-5-Mn (150 mg/kg/day, bid) groups were treated for 7 weeks; preventive group (Is-5-Mn + CsA): Is-5-Mn during 2 weeks plus 7 weeks of Is-5-Mn + CsA; regressive group (CsA + Is-5-Mn): CsA during 7 weeks plus 5 weeks of CsA + Is-5-Mn. The increased BP in the CsA group was prevented, but was not reverted, by concomitant Is-5-Mn treatment. In the CsA-treated rats, there was a noticeable decrease in left ventricle NE and E contents and aorta NE levels and a moderate increase in circulating catecholamines, without significant effect in the adrenals values. When Is-5-Mn was preventively used, the CsA-induced effect on left ventricle and aorta was prevented. Concomitantly, however, the plasma-platelet catecholamine balance was disrupted, accumulating NE in plasma, whereas E increased in aorta, mimic the single Is-5-Mn-treated group. In opposition, in the group used as regressive Is-5-Mn therapy, the adrenals contents were higher compared with the CsA-group and, simultaneously, the CsA-evoked effects on circulating, left ventricle and aorta catecholamines were not reverted. In conclusion, regressive Is-5-Mn therapy was unable to attenuate CsA-induced catecholamine changes and BP values even worsened. On the contrary, preventive Is-5-Mn treatment prevented the catecholamine changes on left ventricle and aorta, but increased plasma NE and aorta E accumulation. Even though with those effects, hypertension development was totally prevented, suggesting that peripheral SNS per se cannot fully explain CsA-induced hypertension. Furthermore, Is-5-Mn might produce beneficial effects only if preventively employed but, considering the changes on peripheral catecholamine contents, a judicious evaluation of the nitrate therapy impact is recommended in order to avoid further deleterious effects. |
publishDate |
2005 |
dc.date.none.fl_str_mv |
2005 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/4758 http://hdl.handle.net/10316/4758 https://doi.org/10.1016/j.lfs.2005.01.032 |
url |
http://hdl.handle.net/10316/4758 https://doi.org/10.1016/j.lfs.2005.01.032 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Life Sciences. 77:20 (2005) 2514-2528 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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