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. 2019 Jul 17;8(15):e012273. doi: 10.1161/JAHA.119.012273

Figure 4.

Figure 4

Sildenafil rescues cyclic nucleotide concentration, increases PKA (protein kinase A) activity, and improves adrenergic E‐C coupling response in a PKG (protein kinase G)– and calcium/calmodulin kinase II–dependent manner. Average maximal fluorescence resonant energy transfer (FRET) response of the cGMP probe, cGi500 in adult ventriculomyocytes (AVMs) from gavaged mice (A) and from young 8‐week‐old mice (B). Average maximal FRET response of the cAMP probe, EpacSH187 in AVMs from gavaged mice (C) and from young 8‐week‐old mice (D). Average maximal FRET response of the PKA activity probe, A‐kinase activity reporter‐3 in AVMs from gavaged mice (E). In all FRET response graphs, n≥15 cells per group; *P≤0.05, **P≤0.01, ***P≤0.001, and ****P≤0.0001 by 1‐way ANOVA with Tukey post‐test. Contractility (F), calcium transient amplitude (G), and calcium transient tau (H) of AVMs from wild‐type mice fed an HFD for 4.5 months. Cells were pretreated with and without DT2 peptide, myrisoylated PKI peptide (PKI), or KN93 before stimulation with isoproterenol and sildenafil. *P≤0.05, **P≤0.01, ***P≤0.001, ****P≤0.0001 by 1‐way ANOVA and Tukey post‐test. n≥25 cells per group.