The Effect Of Endogenous Bradykinin On Hypertrophy Of Neonatal Rat Cardiomyocytes Inducded By Angiotensin I

BACKGROUND AND OBJECTIVES The renin–angiotensin system (RAS) and the kallikrein–kinin system (KKS) each encompasses a large number of molecules that participate in many diverse aspects of physiology and pathophysiology. Bradykinin and angiotensin (Ang) II are important peptides involved in the regulation of vascular tone. Ang II is a vasoconstrictor and growth-promoting substance, whereas bradykinin is a potent vasodilator and growth inhibitor. ACE inhibitors, which are now widely used for the treatment of hypertension and heart failure, not only block the generation of Ang II from Ang I, but also prevent the degradation of bradykinin. In this study,we used method of cultured rat neonatal cardiomyocytes in vitro, observed the Ang I, ACEI captopril, Ang II receptor antagonist losartan, and bradykinin B2 receptor antagonist HOE-140 on the cardiomyocytes hypertrophy, to study the effects of endogenous bradykinin on rat neonatal cardiomyocytes hypertrophy induced by Ang I. METHODS Cardiomyocytes is the major cell type in the heart, and that the pathological process of cardiac hypertrophy and remodeling is based on hypertrophy of cardiomyocytes. Ang I was used to treat neonatal rat cardiomyocytes cultured in serum-free medium and their effects on incorporation of 3H-Leu, total protein content, cellular volume, pulsatile frequency. By 3H-Leu incorporation, model of hypertrophied cardiomyocytes was assessed. The cardiomyocytes'volumes was measured by image analysis program. The pulsatile frequency of cultured myocytes was counted by the inverted microscope. The total protein of cell was measured by the methods of Coomassie Brilliant Blue. RESULTS 1.Ang I dose-dependently induced hypertrophy of cultured neonatal rat cardiomyocytes in serum-free medium. 10^-6 mol/L of Ang I group was compared with the control group, the incorporation of 3H-Leu, total protein content, cellular volume, pulsatile frequency were increased to 49.91%, 89.76%, 77.69% and 39.04%. There are significant differerence (P<0.01). There is resemblance between the Ang I (10^-6 mol/L) induced hypertrophy of cultured neonatal rat cardiomyocytes and Ang II(10^-7 mol/L). 2.Losartan could inhibit the effect of Ang I on hypertrophy of cultured neonatal rat cardiomyocytes. Compared with the Ang I(7d) group, the incorporation of 3^H-Leu, total protein content, cellular volume, pulsatile frequency were decreased to 18.63%, 18.86%, 27.18 % and 26.37% ,respectively. Captopril has similarity role, compared with the Ang (I7d) group, the incorporation of 3H-Leu, total protein content, cellular volume, pulsatile frequency were decreased to 38.76%, 30.28%, 36.80 % and 24.18% ,respectively. There are significant differerence (P<0.01). Compared with the Ang I(3d)group, the incorporation of 3^H-Leu, total protein content, cellular volume, were decreased to 15.94%, 16.81%, 32.06%, respectively. There are significant differerence (P<0.01). 3.The inhibitory effects of ACEI captopril were completely blocked by pretreatment with HOE-140, a specific bradykinin B2 receptor antagonist, also were abolished by nitric oxide synthesis inhibitor nitro-L-arginine(L-NNA). CONCLUSION Ang Ⅰcan transform Ang Ⅱwhich shows that it exists ACE in cultured neonatal rat cardiomyocytes. Ang Ⅰcan increase the total protein content and cellular volume, the effects of ACEI are due to both blockade of Ang Ⅱformation and inhibition of BK degradation. The effect mechanism of ACEI is possible through NO to come ture.