3.2.1. Heart Weight

The relative heart weight (HW/BW) of ySHRs was 3.50 ± 0.07 mg/g without therapy and 3.06 ± 0.06 mg/g (*p* = 0.331) after 3 weeks of C+N therapy, which is a treatment effect of 12.6 ± 1.6%. In untreated oSHRs, HW/BW was significantly higher (5.51 ± 0.51 mg/g, *p* < 0.001), but 22 weeks of C+N treatment significantly reduced HW/BW to 3.44 ± 0.20 mg/g (*p* < 0.001), which is in a similar range as HW/BW of yCtrl rats (Figure 2A). The treatment effect was with 37.4 ± 3.7%, significantly greater than in ySHRs (*p* < 0.005; Figure 2B).

However, the body weight (BW) of the animals changed in a different way; while BW in 10-week-old SHRs was similar in the untreated and treated groups (309.7 ± 7.3 and 308.0 ± 7.3 g, respectively), 82-week-old untreated SHRs had a considerably lower BW (377.6 ± 37.2 g) than age-matched C+N-treated rats (418.6 ± 5.4 g; *p* = 0.042; Table 1). Moreover, SHRs aged 7–10 weeks are still juvenile, and their HW/BW ratio is substantially different from that of old SHRs aged 60–82 weeks. Therefore, analysis of the absolute HW may provide more realistic information about the treatment effects (Figure 2C,D). In

ySHRs, HW was 1095 ± 40 mg in untreated SHRs and 934 ± 28 mg in C+N-treated animals (*p* = 0.136), which means a treatment effect of 14.7 ± 2.6%. In 82-week-old untreated SHRs, HW was significantly higher than in young animals (*p* < 0.001). Twenty-two weeks of C+N treatment significantly decreased HW from 1860 ± 93 mg to 1440 ± 81 mg (*p* < 0.001) corresponding to a treatment effect of 26.8 ± 1.3%. Although this treatment effect was significantly greater than in ySHRs (*p* = 0.035), HW of treated oSHRs remained significantly higher than in ySHRs after only 3 weeks of treatment (*p* < 0.001).

**Figure 1.** (**A**) Systolic blood pressure (in mmHg) at 10 (young SHR) or 82 (old SHR) weeks of age in untreated (Ctrl) and treated (captopril + nifedipine, C+N) SHRs. (**B**) Treatment effects in young and old SHRs (in % of corresponding average Ctrl value). Significance marks: \* significant difference between marked groups, \*\*\* *p* < 0.001; ### significant difference to corresponding young SHR group, *p* < 0.001.

To assess to what extent the treatment effect on HW is mediated by SBP reduction, we further calculated HW reduction per unit SBP reduction. While in yC+N rats, HW decreased by 3.5 ± 0.7 mg/mmHg, this ratio was significantly greater in oC+N animals (9.7 ± 2.1 mg/mmHg, *p* = 0.035; data not shown).
