3.3.2. Fibrosis

Mild to moderate histological signs of fibrosis were already observed in 10-week-old untreated SHRs (fibrosis degree: 1.47 ± 0.12). Three weeks of treatment reduced the degree of fibrosis to 0.59 ± 0.17; *p* < 0.001. The treatment effect was 58.0 ± 11.9%.

Age had a significant effect on the degree of fibrosis. Untreated SHRs aged 82 weeks presented moderate to severe signs of fibrosis (fibrosis degree: 2.30 ± 0.11), which was significantly higher than in ySHRs (*p* < 0.001). After 22 weeks of treatment, there were still signs of moderate fibrosis (fibrosis degree: 2.13 ± 0.07) corresponding to a treatment effect of 7.5 ± 3.1%, which was significantly smaller than that in ySHRs (*p* < 0.001; Figure 5).

**Figure 3.** (**A**) mRNA expression of atrial natriuretic peptide in untreated (Ctrl) and treated (C+N) young and old 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.

**Figure 4.** (**A**) mRNA expression of collagen type I in untreated (Ctrl) and treated (C+N) young and old SHRs. (**B**) Treatment effects on Coll 1 in young and old SHRs (in % of corresponding average Ctrl value). (**C**) mRNA expression of collagen type III in untreated (Ctrl) and treated (C+N) young and old SHRs. (**D**) Treatment effects on Coll 3 in young and old SHRs (in % of corresponding average Ctrl value). Significance marks: \* significant difference between marked groups, \*\* *p* < 0.01, \*\*\* *p* < 0.001; ## significant difference to corresponding young SHR group, *p* < 0.01.

#### **4. Discussion**

It is widely accepted that antihypertensive treatment should start as early in life as possible [3]. Epidemiological studies in humans have shown that young people with high BP were at higher risk of LV hypertrophy and cardiovascular disease events compared with normotensive persons [15–17]. Animal studies have shown that early-onset treatment exerts better effects with respect to SBP and cardioprotection than a therapy started at an advanced age [24,25]. However, only few studies have directly compared the effects of antihypertensive treatment in young and senescent SHRs.
