IDENTIFICATION AND ACTIVATION OF AUTOCRINE RENIN-ANGIOTENSIN SYSTEM IN ADULT VENTRICULAR MYOCYTES

To date, the demonstration that the molecular components of the renin- angiotensin system (RAS) are present in adult ventricular myocytes is lacking. In addition, whether the RAS is upregulated under conditions of overload and myocyte hypertrophy in vivo remains to be determined. By employing an in vivo model of ischemic cardiomyopathy in rats, we d ocument that adult myocytes express genes for renin, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II (ANG II) recep tors. Moreover, renin, ACE, and ANG II receptor mRNAs increased in str essed myocytes undergoing cellular hypertrophy. At the protein level, the percentage of myocytes containing renin, ANG I, and ANG II was sig nificantly increased in the overloaded heart. The number of binding si tes for ANG II per myocyte also markedly increased under this setting. These results provide direct evidence of the existence of a myocyte R AS, which may be activated in pathological states of the heart to supp ort myocyte growth and contractile function.