Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats
- Autores
- Marañón, Rodrigo Oscar; Moulana, Mohadetheh
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- In recent decades, the roles of tacrolimus and mycophenolate mofetil (MMF) in hypertension have been under discussion. However, the question of whether there are sex-specific responses to these agents has not received enough attention. Aim: To evaluate sex-specific differences in the responses to tacrolimus and mycophenolate mofetil in female (F) and male (M) spontaneously hypertensive rats (SHRs) and evaluate whether T cells contribute to mean arterial pressure (MAP) changes. Methods: Male and female SHRs received either tacrolimus or MMF for 14 days. The rats were implanted with radiotelemeters. MAP was measured chronically; then, circulating and renal infiltrated CD4+, CD8+, T helper 17 (Th17), and T regulatory (Treg) cells were quantified using flow cytometry. Key Findings: Tacrolimus increased MAP only in males, and it decreased CD4+ and CD8+ T cells in both males and females (p < 0.05). The tacrolimus-induced reduction of renal CD4+ and Treg cells was more profound in males. MMF reduced MAP and circulating and renal CD4+ and CD8+ T cells in the male and female rats. MMF also decreased Th17 and Treg cells in both sexes, but the decrease in Th17 was higher in males (p < 0.05) and the reduction in Treg cells was higher in females (p < 0.05). Our findings indicate that the effects of tacrolimus and MMF on renal T cell subsets are sex-specific. Significance: Targeting T cells in hypertension using therapeutic agents may have different effects on men and women; so, the management of hypertension and post-transplant hypertension using these agents should be specified by gender.
Fil: Marañón, Rodrigo Oscar. Universidad Nacional de Tucumán. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Moulana, Mohadetheh. University of Mississippi; Estados Unidos - Materia
-
hypertension
sex-differences
spontaneously hypertensive rats
tacrolimus
mycophenolate mofetil - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/240374
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oai:ri.conicet.gov.ar:11336/240374 |
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spelling |
Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive RatsMarañón, Rodrigo OscarMoulana, Mohadethehhypertensionsex-differencesspontaneously hypertensive ratstacrolimusmycophenolate mofetilhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In recent decades, the roles of tacrolimus and mycophenolate mofetil (MMF) in hypertension have been under discussion. However, the question of whether there are sex-specific responses to these agents has not received enough attention. Aim: To evaluate sex-specific differences in the responses to tacrolimus and mycophenolate mofetil in female (F) and male (M) spontaneously hypertensive rats (SHRs) and evaluate whether T cells contribute to mean arterial pressure (MAP) changes. Methods: Male and female SHRs received either tacrolimus or MMF for 14 days. The rats were implanted with radiotelemeters. MAP was measured chronically; then, circulating and renal infiltrated CD4+, CD8+, T helper 17 (Th17), and T regulatory (Treg) cells were quantified using flow cytometry. Key Findings: Tacrolimus increased MAP only in males, and it decreased CD4+ and CD8+ T cells in both males and females (p < 0.05). The tacrolimus-induced reduction of renal CD4+ and Treg cells was more profound in males. MMF reduced MAP and circulating and renal CD4+ and CD8+ T cells in the male and female rats. MMF also decreased Th17 and Treg cells in both sexes, but the decrease in Th17 was higher in males (p < 0.05) and the reduction in Treg cells was higher in females (p < 0.05). Our findings indicate that the effects of tacrolimus and MMF on renal T cell subsets are sex-specific. Significance: Targeting T cells in hypertension using therapeutic agents may have different effects on men and women; so, the management of hypertension and post-transplant hypertension using these agents should be specified by gender.Fil: Marañón, Rodrigo Oscar. Universidad Nacional de Tucumán. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Moulana, Mohadetheh. University of Mississippi; Estados UnidosMDPI2023-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/240374Marañón, Rodrigo Oscar; Moulana, Mohadetheh; Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats; MDPI; Future Pharmacology; 3; 4; 11-2023; 862-8762673-9879CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2673-9879/3/4/52info:eu-repo/semantics/altIdentifier/doi/10.3390/futurepharmacol3040052info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:51Zoai:ri.conicet.gov.ar:11336/240374instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:59:51.868CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats |
title |
Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats |
spellingShingle |
Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats Marañón, Rodrigo Oscar hypertension sex-differences spontaneously hypertensive rats tacrolimus mycophenolate mofetil |
title_short |
Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats |
title_full |
Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats |
title_fullStr |
Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats |
title_full_unstemmed |
Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats |
title_sort |
Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats |
dc.creator.none.fl_str_mv |
Marañón, Rodrigo Oscar Moulana, Mohadetheh |
author |
Marañón, Rodrigo Oscar |
author_facet |
Marañón, Rodrigo Oscar Moulana, Mohadetheh |
author_role |
author |
author2 |
Moulana, Mohadetheh |
author2_role |
author |
dc.subject.none.fl_str_mv |
hypertension sex-differences spontaneously hypertensive rats tacrolimus mycophenolate mofetil |
topic |
hypertension sex-differences spontaneously hypertensive rats tacrolimus mycophenolate mofetil |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
In recent decades, the roles of tacrolimus and mycophenolate mofetil (MMF) in hypertension have been under discussion. However, the question of whether there are sex-specific responses to these agents has not received enough attention. Aim: To evaluate sex-specific differences in the responses to tacrolimus and mycophenolate mofetil in female (F) and male (M) spontaneously hypertensive rats (SHRs) and evaluate whether T cells contribute to mean arterial pressure (MAP) changes. Methods: Male and female SHRs received either tacrolimus or MMF for 14 days. The rats were implanted with radiotelemeters. MAP was measured chronically; then, circulating and renal infiltrated CD4+, CD8+, T helper 17 (Th17), and T regulatory (Treg) cells were quantified using flow cytometry. Key Findings: Tacrolimus increased MAP only in males, and it decreased CD4+ and CD8+ T cells in both males and females (p < 0.05). The tacrolimus-induced reduction of renal CD4+ and Treg cells was more profound in males. MMF reduced MAP and circulating and renal CD4+ and CD8+ T cells in the male and female rats. MMF also decreased Th17 and Treg cells in both sexes, but the decrease in Th17 was higher in males (p < 0.05) and the reduction in Treg cells was higher in females (p < 0.05). Our findings indicate that the effects of tacrolimus and MMF on renal T cell subsets are sex-specific. Significance: Targeting T cells in hypertension using therapeutic agents may have different effects on men and women; so, the management of hypertension and post-transplant hypertension using these agents should be specified by gender. Fil: Marañón, Rodrigo Oscar. Universidad Nacional de Tucumán. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina Fil: Moulana, Mohadetheh. University of Mississippi; Estados Unidos |
description |
In recent decades, the roles of tacrolimus and mycophenolate mofetil (MMF) in hypertension have been under discussion. However, the question of whether there are sex-specific responses to these agents has not received enough attention. Aim: To evaluate sex-specific differences in the responses to tacrolimus and mycophenolate mofetil in female (F) and male (M) spontaneously hypertensive rats (SHRs) and evaluate whether T cells contribute to mean arterial pressure (MAP) changes. Methods: Male and female SHRs received either tacrolimus or MMF for 14 days. The rats were implanted with radiotelemeters. MAP was measured chronically; then, circulating and renal infiltrated CD4+, CD8+, T helper 17 (Th17), and T regulatory (Treg) cells were quantified using flow cytometry. Key Findings: Tacrolimus increased MAP only in males, and it decreased CD4+ and CD8+ T cells in both males and females (p < 0.05). The tacrolimus-induced reduction of renal CD4+ and Treg cells was more profound in males. MMF reduced MAP and circulating and renal CD4+ and CD8+ T cells in the male and female rats. MMF also decreased Th17 and Treg cells in both sexes, but the decrease in Th17 was higher in males (p < 0.05) and the reduction in Treg cells was higher in females (p < 0.05). Our findings indicate that the effects of tacrolimus and MMF on renal T cell subsets are sex-specific. Significance: Targeting T cells in hypertension using therapeutic agents may have different effects on men and women; so, the management of hypertension and post-transplant hypertension using these agents should be specified by gender. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-11 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/240374 Marañón, Rodrigo Oscar; Moulana, Mohadetheh; Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats; MDPI; Future Pharmacology; 3; 4; 11-2023; 862-876 2673-9879 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/240374 |
identifier_str_mv |
Marañón, Rodrigo Oscar; Moulana, Mohadetheh; Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats; MDPI; Future Pharmacology; 3; 4; 11-2023; 862-876 2673-9879 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2673-9879/3/4/52 info:eu-repo/semantics/altIdentifier/doi/10.3390/futurepharmacol3040052 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1842269606178193408 |
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13.13397 |