OBJECTIVETo 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).

METHODSMale 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.

RESULTSAt 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).

CONCLUSIONSLong-term ADM treatment can control SPB elevation in SHR rats and reduce renal arteriole remodeling by inhibiting the phosphorylation of ERK1/2.