The Research Of Effect Of Adrenomedullin On Cardiovascular Remodeling Of SHR And Its Relationship With P-ERK1/2

Objective To investigate the effect of adrenomedullin on remodeling of heart、aorta、renal arteriole in spontaneous hypertension rat (SHR), and relationship between theinfluence and p-ERK1/2expression.Methods Thirty-two4week-old male SHR were randomized grouped into hypertension(SHR) group and SHR treatment group (SHR-T), age matched16Wistar Kyota rats (WKY)as control. SHR-T group rats were subcutaneously injected with ADM (5days/week,1.0nmol/kg.d), SHR group rats only with matched volum saline. WKY rats without anytreatment as a blank control.Tail-cuff systolic blood pressure (SBP) was measured every week.Heart, aorta and kidney were harvested after rats sacrificed at4、8、16、24week-old. Themorphological changes of heart, aorta and renal vascular remodeling were observed by H.E,elastic fiber staining and electron microscope. P-ERK1/2was detected byimmunohistochemistry and western blotting.Results From8weeks old, SBP level of SHR group and SHR-T group started higherthan WKY group (P <0.01).However, decreased SBP was detected in at24week SHR-Tgroup than SHR group(P<0.05). Hypertrophy of left ventricular wall, thickening and stenosisvascular wall of aorta and renal arteriole appeared at8week-old SHR. SBP、 heartweight(HW)/body weight(BW)、relative left ventricular wall thickness (RLVWT)(leftventricular wall thickness/maximum ventricular diameter)、media thickness (MT)/lumendiameter (LD) of renal15-40microns arteriole At24week-old SHR-T group decreasedcompare with that of SHR group(P <0.05). Electron microscope showed that obviously degeneration of vascular endothelial cell and hypertrophy of VSMC appeared at SHR groupaortal.ADM can attenuated these abnormal changes to some extent.IHC and WB showed thatp-ERK1/2express quantity of24old-week SHR group heart、aorta、renal arteriole(outerdiameter15-40microns and40-85microns)increase than WKY group(P<0.05),and SHR-Tgroup decrease than SHR group(P<0.05).Conclusions To some extent，ADM effectively decreased SHR SBP and attenuatedcardiovascular remodeling induced by hypertension. It is different that effect of ADM reverseaorta and renal arteriole remodeling. It is more effective to alleviate small arterioleremodeling.ADM might play cardioprotective protective action through decrease p-ERK1/2expression.