Fig. 4. Altered relaxation of vascular smooth muscle cells by increased blood amylin concentrations.

a T₂-weighted MRI and longitudinal ventricular hyperintensity volumes in HIP vs. WT rats (n = 4–5 males/group). b CBF maps and global CBF in HIP and WT rats, age 15-16 months (9 males/group). c Cross-sectional concentrations of plasma nitrite and nitrate in HIP and WT rats (n = 6 males/group/age). Diameter traces in pial arteries from HIP and WT rat males at different intravascular pressures (d), and arterial tone of pial arteries (e) measured at the indicated intravascular pressure (2–3 arteries/ rat, n = 6–7 males/group, age 15–16 months). f Same as in (e) in posterior cerebral arteries from WT and amylin knockout (AKO) rats, and in AKO rats intravenously injected with human amylin (n = 3 males/group, age 9–10 months). g, h Lipid peroxidation in pial artery SMCs from WT and diabetic HIP rat males measured with Liperfluo (g; N = 62 SMC from 4 WT rats and 70 cells from 4 HIP rats) and C₁₁-BODIPY^581/591 (h; N = 87 SMC from 7 WT rats and 68 cells from 4 HIP rats). i Arginase activity and arginase-1 and arginase-2 concentrations in HIP vs. WT brain microvessel lysates (n = 7 males/group; age 15–16 months). j Proposed mechanism: chronically increased concentrations of pancreatic amyloid-forming amylin in blood cause oxidative stress within the vascular wall leading to NO-arginase dysregulation and impaired SMC function and myogenic tone. Data are means ± SEM. Mann–Whitney non-parametric test for panels (g, h), unpaired t-test for the other panels.