Objective   To study the interventional effects of olmesartan medoxomil (OM) on vascular endothelial function and expressions of ERK/CREB signaling pathway in rats with acute myocardial infarction (AMI).    Methods   Totally 24 rats were randomized equally into AMI group

low dose OM treatment group (OM

L) and high dose treatment group (OMH). After AMI rat model was established by ligating the left anterior descending branch of coronary artery. Another 7 rat who received sham operation served as sham group. In 24 h after operation

the rats from OML group were given an intragastric injection of 1 mg/kg OM once per day

and those of OMH group 3 mg/kg. AMI group only received a treatment of latent solvent at same volume. Two weeks after the interventionall rats were sacrificed after blood pressure was measured

and then levels of blood NO and Ang Ⅱ

activities of NOS

endothelial vasomotor effects of isolated thoracic aorta strips

myocardial infarctual area and the expressions of ERK mRNA and CREB mRNA in infarctual myocardium were detected and measured.    Results   Compared with those in the sham group

levels of serum NO and activities of NOS in AMI group were much lower

NO in sham and AMI group were 55.69±10.40 and 24.46±3.95 μmol/L respectively

and NOS were 23.80±5.36 and 10.92±5.96 U/ml

respectively. Endothelium-dependent diastole (EDD) was decreased markedly

(6.15±0.03)×10

-8

vs (4.45±0.21)×10

-7

mol/L in sham and AMI groups. While the levels of plasma AngⅡin AMI group (281.14±84.90 pg/ml) were distinctly higher than in sham group (181.39±32.70 pg/ml)

accompanied with higher mRNA expressions of ERK1 (0.51±0.09 vs 1.23±0.22) and CREB (0.40±0.19 vs 1.15±0.30) in infarctual myocardium. All of the above differences were significant. After the treatment of OM

levels of serum NO and activities of NOS were obviously higher and almost reached the similar levels as those in sham group. NO was 43.44±14.17 and 46.73±11.30 μmol/L in OML and OMH group

respectively

while NOS were 16.21±5.42 and 18.69±6.73 U/ml. Additionally EDD in isolated aortic strips improved greatly

they were (2.65±0.12)×10-7 and (1.66±1.00)×10

-7

mol/L. OM not only increased the plasma Ang Ⅱ (344.55±76.74 and 511.14±146.65 pg/ml respectively)

but also decreased the size of myocardial infarction and the mRNA e

xpressions of ERK1 (1.02±0.18 and 0.79±0.13) and CREB (0.90±0.18 and 0.65±0.16) in infarctual myocardium in a dose-dependant manner. However

blood pressure in all groups was not affected.    Conclusion   OM can greatly improve the disordered endothelial function developing post-AMI

decrease the size of myocardial infarction and down-regulate the mRNA expressions of ERK and CREB in myocardium of infarctual zone in a dose-dependent manner. And all of the above protective effects of OM are independent on blood pressure lowering.