*3.2. Hydroxyproline Concentration and Content in Soluble and Insoluble Collagen and Total Hydroxyproline in the Left Ventricle*

The hydroxyproline concentrations in the soluble collagenous protein were 0.174 ± 0.008 mg/g and 0.199 ± 0.013 mg/g in the control and SHR groups, respectively (ns). After six weeks of treatment, none of the therapeutics affected the hydroxyproline concentration in the soluble collagenous protein (Figure 2A).

**Figure 2.** Effect of ARNI and ivabradine on hydroxyproline concentration in soluble and insoluble collagenous proteins and on the total hydroxyproline concentration (**A**), and on hydroxyproline content in the soluble and insoluble collagenous proteins, and on the total hydroxyproline content (**B**) in the left ventricle in SHRs after six weeks of treatment. ARNI, sacubitril/valsartan; C, Wistar controls; IVA, ivabradine; SHRs, spontaneously hypertensive rats. Results are presented as means ± SEM. *n* = 15 per group. One-way, two-tailed ANOVA followed by multiple comparisons with a Bonferroni post-hoc test; \* *p* < 0.05 vs. C; # *p* < 0.05 vs. SHR.

The hydroxyproline concentration in the insoluble collagenous protein was 0.578 ± 0.017 mg/g in the control group, and ARNI had no effect after six weeks of treatment. In the SHR group, the hydroxyproline concentration in the insoluble collagenous protein was higher than in controls by 16% (0.673 ± 0.025 mg/g, *p* < 0.05 vs. C), and ARNI and ivabradine decreased it (*p* < 0.05) by 11% and 15%, respectively (Figure 2A).

The total hydroxyproline concentration was 0.752 ± 0.022 mg/g in the control group, and ARNI had no effect after six weeks of treatment. In the SHR group, the total hydroxyproline concentration was higher than in controls by 16% (0.871 ± 0.026 mg/g, *p* < 0.05 vs. C), and ivabradine decreased it (*p* < 0.05) by 11%; ARNI had no significant effect (Figure 2A).

The hydroxyproline content in the soluble collagenous protein was 0.072 ± 0.003 mg/LV in the control group, and ARNI had no effect after six weeks of treatment. In the SHR group, the hydroxyproline content in the soluble collagenous protein was higher than in controls by 50% (0.108 ± 0.007 mg/LV, *p* < 0.05 vs. C), and none of the therapeutics had a significant effect (Figure 2B).

The hydroxyproline content in the insoluble collagenous protein was 0.241 ± 0.012 mg/LV in the control group, and ARNI had no effect after six weeks of treatment. In the SHR group, the hydroxyproline content in the insoluble collagenous protein was higher than in controls by 53% (0.368 ± 0.018 mg/LV, *p* < 0.05 vs. C), and ARNI and ivabradine decreased it (*p* < 0.05) by 24% and 19%, respectively (Figure 2B).

The total hydroxyproline content was 0.313 ± 0.014 mg/LV in the control group, and ARNI had no effect after six weeks of treatment. In the SHR group, the total hydroxyproline content was higher than in controls by 52% (0.476 ± 0.019 mg/LV, *p* < 0.05 vs. C), and ARNI and ivabradine decreased it (*p* < 0.05) by 22% and 15%, respectively (Figure 2B).
