Elevated pulmonary arterial pressure in Zucker diabetic fatty rats

Diabetes is a very strong predictor of chronic systemic vascular diseases and acute cardiovascular events. Recently, associations between metabolic disorders and pulmonary hypertension have also been reported in both humans and animal models. In order to get some further insight into the relationshi...

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Detalhes bibliográficos
Autores: Morales Cano, Daniel, Callejo Arranz, María, Barreira, Bianca, Mondejar Parreño, Gema, Esquivel Ruiz, Sergio Antonio, Ramos, Sonia, Martín Arribas, María Ángeles, Cogolludo Torralba, Ángel Luis, Moreno Gutiérrez, Laura, Pérez Vizcaíno, Francisco
Formato: artículo
Fecha de publicación:2019
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/98139
Acesso em linha:https://hdl.handle.net/20.500.14352/98139
Access Level:acceso abierto
Palavra-chave:612
Fisiología
2411.03 Fisiología Cardiovascular
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spelling Elevated pulmonary arterial pressure in Zucker diabetic fatty ratsMorales Cano, DanielCallejo Arranz, MaríaBarreira, BiancaMondejar Parreño, GemaEsquivel Ruiz, Sergio AntonioRamos, SoniaMartín Arribas, María ÁngelesCogolludo Torralba, Ángel LuisMoreno Gutiérrez, LauraPérez Vizcaíno, Francisco612Fisiología2411.03 Fisiología CardiovascularDiabetes is a very strong predictor of chronic systemic vascular diseases and acute cardiovascular events. Recently, associations between metabolic disorders and pulmonary hypertension have also been reported in both humans and animal models. In order to get some further insight into the relationship of pulmonary hypertension with obesity, insulin resistance and hyperglycemia, herein we have used the Zucker diabetic fatty rats (ZDF/clr-lepr fa) at 20 weeks fed a standard diet and compared to their lean Zucker littermates (ZL). ZDF rats were obese, had elevated plasma glucose levels and insulin resistance, i.e. a clinically relevant model of type 2 diabetes. They presented elevated systolic, diastolic and mean pulmonary arterial pressures and a parallel increase in the Fulton index. Systemic arterial pressures were also increased but the left ventricle plus septum weight was similar in both groups and the heart rate was reduced. Wall media thickening was observed in the small pulmonary arteries from the ZDF rats. Isolated pulmonary arteries mounted in a wire myograph showed similar vasoconstrictor responses to phenylephrine and 5-HT and similar responses to the endothelium-dependent vasodilator acetylcholine. However, the iNOS inhibitor 1400W enhanced the vasoconstrictor responses in ZDF but not in ZL rats. The protein expression of eNOS and iNOS was not significantly different in the lungs of the two groups. The lung expression of Bmpr2 mRNA was downregulated. However, the mRNA expression of Kcna5, Kcnk3, Kcnq1, Kcnq4 or Kcnq5, which encode for the potassium channels Kv1.5, TASK-1, Kv7.1, Kv7.4 and Kv7.5, respectively, was similar in ZL and ZDF rats. In conclusion, ZDF rats show increased pulmonary arterial pressure, right ventricular hypertrophy, pulmonary arterial medial thickening and downregulated lung Bmpr2 despite leptin resistance. These changes were mild but are consistent with the view that diabetes is a risk factor for pulmonary hypertension.Public Library of ScienceBader, MichaelUniversidad Complutense de Madrid20192019-01-2820192019-01-28journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/98139reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/981392026-06-02T12:44:21Z
dc.title.none.fl_str_mv Elevated pulmonary arterial pressure in Zucker diabetic fatty rats
title Elevated pulmonary arterial pressure in Zucker diabetic fatty rats
spellingShingle Elevated pulmonary arterial pressure in Zucker diabetic fatty rats
Morales Cano, Daniel
612
Fisiología
2411.03 Fisiología Cardiovascular
title_short Elevated pulmonary arterial pressure in Zucker diabetic fatty rats
title_full Elevated pulmonary arterial pressure in Zucker diabetic fatty rats
title_fullStr Elevated pulmonary arterial pressure in Zucker diabetic fatty rats
title_full_unstemmed Elevated pulmonary arterial pressure in Zucker diabetic fatty rats
title_sort Elevated pulmonary arterial pressure in Zucker diabetic fatty rats
dc.creator.none.fl_str_mv Morales Cano, Daniel
Callejo Arranz, María
Barreira, Bianca
Mondejar Parreño, Gema
Esquivel Ruiz, Sergio Antonio
Ramos, Sonia
Martín Arribas, María Ángeles
Cogolludo Torralba, Ángel Luis
Moreno Gutiérrez, Laura
Pérez Vizcaíno, Francisco
author Morales Cano, Daniel
author_facet Morales Cano, Daniel
Callejo Arranz, María
Barreira, Bianca
Mondejar Parreño, Gema
Esquivel Ruiz, Sergio Antonio
Ramos, Sonia
Martín Arribas, María Ángeles
Cogolludo Torralba, Ángel Luis
Moreno Gutiérrez, Laura
Pérez Vizcaíno, Francisco
author_role author
author2 Callejo Arranz, María
Barreira, Bianca
Mondejar Parreño, Gema
Esquivel Ruiz, Sergio Antonio
Ramos, Sonia
Martín Arribas, María Ángeles
Cogolludo Torralba, Ángel Luis
Moreno Gutiérrez, Laura
Pérez Vizcaíno, Francisco
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Bader, Michael
Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 612
Fisiología
2411.03 Fisiología Cardiovascular
topic 612
Fisiología
2411.03 Fisiología Cardiovascular
description Diabetes is a very strong predictor of chronic systemic vascular diseases and acute cardiovascular events. Recently, associations between metabolic disorders and pulmonary hypertension have also been reported in both humans and animal models. In order to get some further insight into the relationship of pulmonary hypertension with obesity, insulin resistance and hyperglycemia, herein we have used the Zucker diabetic fatty rats (ZDF/clr-lepr fa) at 20 weeks fed a standard diet and compared to their lean Zucker littermates (ZL). ZDF rats were obese, had elevated plasma glucose levels and insulin resistance, i.e. a clinically relevant model of type 2 diabetes. They presented elevated systolic, diastolic and mean pulmonary arterial pressures and a parallel increase in the Fulton index. Systemic arterial pressures were also increased but the left ventricle plus septum weight was similar in both groups and the heart rate was reduced. Wall media thickening was observed in the small pulmonary arteries from the ZDF rats. Isolated pulmonary arteries mounted in a wire myograph showed similar vasoconstrictor responses to phenylephrine and 5-HT and similar responses to the endothelium-dependent vasodilator acetylcholine. However, the iNOS inhibitor 1400W enhanced the vasoconstrictor responses in ZDF but not in ZL rats. The protein expression of eNOS and iNOS was not significantly different in the lungs of the two groups. The lung expression of Bmpr2 mRNA was downregulated. However, the mRNA expression of Kcna5, Kcnk3, Kcnq1, Kcnq4 or Kcnq5, which encode for the potassium channels Kv1.5, TASK-1, Kv7.1, Kv7.4 and Kv7.5, respectively, was similar in ZL and ZDF rats. In conclusion, ZDF rats show increased pulmonary arterial pressure, right ventricular hypertrophy, pulmonary arterial medial thickening and downregulated lung Bmpr2 despite leptin resistance. These changes were mild but are consistent with the view that diabetes is a risk factor for pulmonary hypertension.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-28
2019
2019-01-28
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/98139
url https://hdl.handle.net/20.500.14352/98139
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,228081

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