Gene expression of brain natriuretic peptide in isolated atrial and ventricular human myocardium - Influence of angiotensin II and diastolic fiber length

Background-We studied the effects of angiotensin II (Ang II) and diastolic overstretch on the induction of cardiac growth in isometrically contracting muscle preparations from human right atria and left ventricles. We used th e gene expression of brain natriuretic peptide (BNP) as a molecular marker of cardiac hypertrophy. Methods and Results-Northern blot analysis was performed in human atrial mu scle preparations, which were either incubated in 10(-6) mol/L Ang II for 4 5 minutes or diastolically stretched to 120% of optimum muscle length. Simi lar experiments were performed with human left ventricular muscle preparati ons. Results were as follows: (1) BNP gene expression increased in human at rial myocardium 4-fold when stimulated by Ang II (n=7, P<0.001). (2) Diasto lic overstretch increased BNP expression in a time-dependent manner. The li near regression equations for the BNP/GAPDH ratio as a function of time (ho urs) were y=1.21+0.62x (P<0.001) for overstretched preparations and y=1.07- 0.01x (P=NS) for atrial preparations kept at physiological muscle length. ( 3) In left ventricular human muscle preparations, diastolic overstretch and Ang II increased BNP gene expression as well. (4) In addition, the Ang II subtype 1 receptor blocker losartan was able to block the effects of Ang II and diastolic overstretch. Conclusions-Cardiac hypertrophy can be induced in isolated human atrial and left ventricular intact myocardium by Ang II and diastolic overstretch but not by isometric afterload. The fact that the induction of cardiac growth is inhibited by the blockade of Ang II subtype 1 receptors is of scientific and clinical importance.