Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K+ Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency

Figures

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  Figure 1. VitD treatment does not reduce mPAP in PAH rats with vitD deficiency. (A) Study protocol. (B) 25(OH)vitD levels; (C) evolution of body weight; (D) mPAP and (E) Fulton index in the groups at the end of the study period. Results are represented as scatter plots and bars with means ± SEM. SuHx-deficit and SuHx-restored indicate rats exposed to Su5416 and hypoxia (SuHx) with vitD-free diet (SuHx-Deficit) and rats with vitD treatment (SuHx-restored), respectively. *** p < 0.001 vs. SuHx-deficit, unpaired t-test.

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  Figure 2. VitD treatment improves endothelial function in isolated PA. (A) Contractile responses to KCl (80 mM). Each dot represents the response of a single artery (2–3 arterial rings per animal). Cumulative concentration-responses curves to (B) serotonin (5-HT); (C) acetylcholine (ACh). Results in Panel A are scatter plots and bars with means ± SEM. Data in Panels B and C are means ± SEM. *** p < 0.001 vs. SuHx-deficit, unpaired t-test.

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  Figure 3. VitD restores Kv currents. (A) Representative currents traces (left) for 250 ms depolarization pulses from −60 mV to +60 mV in 10 mV increments and mean current-voltage relationship of K+ currents measured at the end of the pulse (right). (B) Membrane potential (Em) values in freshly PASMC measured in mV and (C) average cell capacitance from freshly isolated PASMC measured in pF. The parentheses indicate the number of cells and the number of animals from whom these cells were obtained. Results are means ± SEM. * and ** indicate p < 0.05 and p < 0.01, respectively, vs. SuHx-deficit group, unpaired t-test.

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  Figure 4. Restoring vitD levels increases TASK-1 activity. (A) Representative current traces (left) and average data of pH-sensitive currents obtained by measuring the difference in K+ current at external pH values of 7.3 and 6.3 (right). Data are averaged traces (mean ± SEM). (B) Mean values of the pH-sensitive current recorded at 0 mV. Results are expressed as scatter plots and bars; * p < 0.05, unpaired t-test.

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  Figure 5. Lung histology. (A) Representative images of cross-sections of lungs of SuHx-deficit rats (left) and SuHx-restored (right) stained with hematoxylin and eosin. The elastin autofluorescence is shown in the insets. (B) Percentage of muscular, partially muscular, and non-muscular PA. (C) Protein expression of PCNA (proliferating cell nuclear antigen; 29 KDa) analyzed by Western blot, typical blots (bottom panel) and densitometric values and normalized by β-actin (top panel); data are expressed as scatter plots and bars with means ± SEM.