Figure 7. Long-term inhibition of RAS induces arteriolar hypertrophy in mice.

(A) Schematic of the treatments of BPN/3 and BPH/2 mice. After 6 months of treatment with captopril in the drinking water, BUN (B, n ≥ 4), Ren1 mRNA (C, n ≥ 3), and plasma renin (D, n ≥ 5) were significantly increased in both BPN/3 and BPH/2 mice (2-way ANOVA followed by Tukey’s multiple comparison test). (E) The mean blood pressure was significantly decreased by the captopril treatment in both BPN/3 and BPH/2 mice (n ≥ 4, 2-way ANOVA followed by Tukey’s multiple comparison test). Arteriolar hypertrophy induced by renin cells with long-term captopril treatment in BPN/3 mice (F) and BPH/2 mice (G) shown by PAS staining, Masson’s trichrome staining, and immunohistochemistry for renin. Arrows indicate hypertrophic afferent arterioles. Scale bars: 50 μm. Immunohistochemistry for α-SMA showed increased thickness of the walls of afferent arterioles in kidneys from BPN/3 mice (H) and BPH/2 mice (I). The mean wall thickness of afferent arterioles at the JG area was significantly larger in mice with long-term captopril treatment (n = 4, each, Student’s t test). Relative frequency distribution histograms show that the distribution curves corresponding to the mice with captopril treatment are displaced to the right of controls. Scale bars: 50 μm. All data are reported as means ± standard deviation. Triangles represent male samples, and dots female samples. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. BUN, blood urea nitrogen; JG, juxtaglomerular; PAS, periodic acid–Schiff; RAS, renin-angiotensin system.