We examined acute and chronic effects of Ang II on myocardial contractility. Acute Ang II infusion has transient negative inotropic effects on the myocardium. This can be segregated into vascular dependent and direct effects. Direct negative inotropic effects of Ang II are linked to NAD(P)H oxidase activation and subsequent superoxide release. Conversely, to deduce long term effects of Ang II on the myocardium, we obtained a mouse model (Angiotensin Converting Enzyme 2 (ACE2) knockout mice) with increased Ang II levels in the heart, kidneys and plasma. We observed that ACE2 knockout had persistent depressed intrinsic and in vivo contractility and depressed intrinsic coronary flow (when heart weights are included in the calculation). Therefore this thesis reveals that in the mouse, Ang II either through acute or chronic experimental situations has negative inotropic effects on contractility and these effects are mediated either through vascular dependent or direct effects of Ang II.