RT Journal Article
T1 Elevated pulmonary arterial pressure in Zucker diabetic fatty rats
A1 Morales Cano, Daniel
A1 Callejo Arranz, María
A1 Barreira, Bianca
A1 Mondejar Parreño, Gema
A1 Esquivel Ruiz, Sergio Antonio
A1 Ramos, Sonia
A1 Martín Arribas, María Ángeles
A1 Cogolludo, Angel
A1 Moreno Gutiérrez, Laura
A1 Pérez Vizcaíno, Francisco
A2 Bader, Michael
AB 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.
PB Public Library of Science
SN 1932-6203
YR 2019
FD 2019-01-28
LK https://hdl.handle.net/20.500.14352/98139
UL https://hdl.handle.net/20.500.14352/98139
LA eng
NO Morales-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
NO Unión Europea
NO Ministerio de Economía y Competitividad
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 18 jul 2024