Compensatory function of bradykinin B1 receptor in the inhibitory effect of captopril on cardiomyocyte hypertrophy and cardiac fibroblast proliferation in neonatal rats

• Published in: Chinese medical journal Vol. 121; no. 13; pp. 1220 - 1225
• Main Authors: Zou, Jun, Ren, Jiang-hua, Feng, Dan, Wang, Hong, Xu, Jiang
• Format: Journal Article
• Language: English
• Published: China Department of Cardiology,Zhongnan Hospital of Wuhan University,Wuhan,Hubei 430071,China%Department of Physiology,Medical College of Wuhan University,Wuban,Hubei 430071,China 05.07.2008
• Subjects: Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Animals, Newborn; Captopril - pharmacology; Cardiomegaly - prevention & control; Cell Proliferation - drug effects; Cell Size - drug effects; Cyclic GMP - analysis; DNA - biosynthesis; Fibroblasts - drug effects; Fibroblasts - physiology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - pathology; Nitric Oxide - analysis; Rats; Rats, Sprague-Dawley; Receptor, Bradykinin B1 - physiology; 强心剂; 心肌症; 成纤维细胞; 缓激肽; bradykinin; cardiac fibroblast; captopril; cardiomyocyte
• ISSN: 0366-6999; 2542-5641
• DOI: 10.1097/00029330-200807010-00014

Background Bradykinin （BK） acts mainly on two receptor subtypes： B1 and B2, and activation of B2 receptor mediates the most well-known cardioprotective effects of angiotensin converting enzyme inhibitors （ACEi）, however, the role that B1 receptor plays in ACEi has not been fully defined. We examined the role of B1 receptor in the inhibitory effect of ACE inhibitor captopril on rat cardiomyocyte hypertrophy and cardiac fibroblast proliferation induced by angiotensin Ⅱ （Ang Ⅱ） and explored its possible mechanism. Methods Neonatal cardiomyocytes and cardiac fibroblasts （CFs） were randomly treated with Ang Ⅱ, captopdl, B2 receptor antagonist （HOE-140） and B1 receptor antagonist （des-Arg^10, Leu^9-kallidin） alone or in combination. Flow cytometry was used to evaluate cell cycle, size and protein content. Nitric oxide （NO） and intracellular cyclic guanosine monophosphate （cGMP） level were measured by colorimetry and radioimmunoassay. Results After the CFs and cardiomyocytes were incubated with 0.1 μmol/L Ang Ⅱ for 48 hours, the percentage of CFs in the S stage, cardiomyocytes size and protein content significantly increased （both P 〈0.01 vs control）, and these increases were inhibited by 10 μmol/L captopril. However, NO and cGMP levels were significantly higher than that with Ang Ⅱ alone （both P 〈0.01）. 1 μmol/L HOE-140 or 0.1 pmol/L des-Arg^10, Leu^9-kallidin attenuated the effects of captopril, which was blunted further by blockade of both B1 and B2 receptors. Conclusions Acting via B2 receptor, BK contributes to the antihypertrophic and antiproliferative effects of captopril on cardiomyocytes and CFs. In the absence of B2 receptor, B1 receptor may act a compensatory mechanism for the B2 receptor and contribute to the inhibition of cardiomyocyte hypertrophy and CFs proliferation by captopril. NO and cGMP play an important role in the effect of B1 receptor.