Cardiac angiotensin II: does it have a function?

ANGIOTENSIN (ANG) II, in addition to its vasoconstrictor effects, is believed to be a direct mediator of left ventricular hypertro-phy and cardiac fibrosis, thus explaining the beneficial cardiac effects of renin-angiotensin system (RAS) blockers in humans. Yet, simultaneously, it has been argued that these effects can simply be attributed to the blood pressure-lowering capacity of RAS blockers. A critical review recently concluded that the bulk of evidence, obtained in genetically modified experimen-tal animals [e.g., overexpressing angiotensinogen, angiotensin-converting enzyme (ACE), or ANG II type 1 (AT1) receptors in the heart], does not support a direct role of the RAS in left ventricular hypertrophy (18). In fact, even transgenic mice expressing an engineered fusion protein designed to directly release ANG II in the heart (using the -myosin heavy chain promoter), despite having 20- to 50-fold elevated cardiac ANG