Elevated pulmonary arterial pressure in Zucker diabetic fatty rats

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dc.contributor.authorMorales Cano, Daniel
dc.contributor.authorCallejo Arranz, María
dc.contributor.authorBarreira, Bianca
dc.contributor.authorMondejar Parreño, Gema
dc.contributor.authorEsquivel Ruiz, Sergio Antonio
dc.contributor.authorRamos, Sonia
dc.contributor.authorMartín Arribas, María Ángeles
dc.contributor.authorCogolludo, Angel
dc.contributor.authorMoreno Gutiérrez, Laura
dc.contributor.authorPérez Vizcaíno, Francisco
dc.contributor.editorBader, Michael
dc.date.accessioned2024-02-02T09:53:14Z
dc.date.available2024-02-02T09:53:14Z
dc.date.issued2019-01-28
dc.description.abstractDiabetes 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.
dc.description.departmentDepto. de Farmacología y Toxicología
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipUnión Europea
dc.description.sponsorshipMinisterio de Economía y Competitividad
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.statuspub
dc.identifier.citationMorales-Cano D, Callejo M, Barreira B, Mondejar-Parreño G, Esquivel-Ruiz S, Ramos S, Martín MÁ, Cogolludo A, Moreno L, Perez-Vizcaino F. Elevated pulmonary arterial pressure in Zucker diabetic fatty rats. PLoS One. 2019 Jan 28;14(1):e0211281. doi: 10.1371/journal.pone.0211281
dc.identifier.doi10.1371/journal.pone.0211281
dc.identifier.issn1932-6203
dc.identifier.officialurlhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211281
dc.identifier.pmid30689673
dc.identifier.relatedurlhttps://pubmed.ncbi.nlm.nih.gov/30689673/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/98139
dc.issue.number1
dc.journal.titlePLoS ONE
dc.language.isoeng
dc.publisherPublic Library of Science
dc.relation.projectIDFEDER
dc.relation.projectIDSAF2016-77222-R
dc.relation.projectIDAGL2015–67087-R
dc.relation.projectIDPI15/01100
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu612
dc.subject.ucmFisiología
dc.subject.unesco2411.03 Fisiología Cardiovascular
dc.titleElevated pulmonary arterial pressure in Zucker diabetic fatty rats
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number14
dspace.entity.typePublication
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