OBJECTIVETo evaluate the inhibitory effect and related mechanism of bradykinin on mechanical stress induced myocardial hypertrophy.

METHODSNeonatal rat cardiomyocytes were isolated and cultured in silicon plates. All cardiomyocytes were randomly divided into three groups: control group, mechanical stretch group (mechanical stretch of silicon plates to 120% for 30 min) and mechanical stretch plus bradykinin group (1×10(-8) mol/L for 24 h before stretch). The protein synthesis and surface area of cardiomyocytes were detected by [(3)H] leucine incorporation and immunofluorescence of α-MHC, respectively. mRNA expression of atrial natriuretic peptide (ANP) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) was detected by real time-PCR, the phosphorylation of calcineurin (CaN), the expression of Angiotensin II receptor 1 (AT1R) and angiotensin converting enzyme (ACE)by Western blot.

RESULTSThe surface area of cardiomyocytes of mechanical stretch group [(973 ± 103) µm(2)] was significantly enlarged than in control group [(312 ± 29) µm(2)] and this effect could be partly attenuated by bradykinin [(603 ± 74) µm(2), all P < 0.05]. Mechanical stretch also significantly increased the protein synthesis, up-regulated the expression of ANP and decreased the expression of SERCA2, and these effects could be partly reversed by pretreatment with bradykinin. Moreover, bradykinin partly abolished the mechanical stretch-induced increases in CaN phosphorylation, up-regulation of AT1R but preserved the expression of ACE.

CONCLUSIONSBradykinin significantly attenuates mechanical stretch-induced myocardial hypertrophy through inhibition of Ca(2+)/CaN pathway.