Abstract: Objective To investigate the effect of adrenomedullin (ADM) on renal arteriole remodeling and phosphorylation of
extracellular signal-regulated protein kinases 1/2 (p-ERK1/2) in spontaneous hypertensive rats (SHR). Methods Male SHR (4
weeks old) were randomized into hypertensive group (SHR) and ADM-treated group (ADM) to receive subcutaneous saline
and ADM injections (daily dose of 1.0 nmol/kg, 5 days a week), respectively, with age-matched Wistar-Kyota (WKY) rats as the
blank control. The systolic blood pressure (SBP) was measured at the end of each week, and histological changes of the renal
arterioles were observed using HE and Weigert staining; the expression of P-ERK1/2 in the arterioles was detected with
immunohistochemistry and Western blotting. Results At 16 and 24 weeks of age, the rats in both SHR and ADM groups
showed significantly higher SBP levels than WKY rats (P<0.05), and at 24 weeks, SBP was significantly lower in ADM group
than in SHR group (P<0.05). The intima thickness/lumen diameter (IT/LD) ratio of the renal arterioles increased in both SHR
and ADM groups at 16 and 24 weeks as compared with that of WKY rats (P<0.05), and for arterioles with an outer diameter <40
μm, the IT/LD ratio was significantly lower at 24 weeks in ADM group than in SHR group (P<0.05). The renal expression of
p-ERK1/2, which increased significantly in SHR and ADM groups at 16 and 24 weeks (P<0.05), was significantly lower in ADM
group than in SHR group at 24 weeks (P<0.05). Conclusions Long-term ADM treatment can control SPB elevation in SHR rats
and reduce renal arteriole remodeling by inhibiting the phosphorylation of ERK1/2.