Objective: To evaluate the inhibitory effect and related mechanism of bradykinin on mechanical stress induced myocardial hypertrophy.
Methods: Neonatal 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.
Results: The 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.
Conclusions: Bradykinin significantly attenuates mechanical stretch-induced myocardial hypertrophy through inhibition of Ca(2+)/CaN pathway.