A sudden increase in afterload on the heart causes an increase in ventricular inotropy. This is called the Anrep effect. The phenomenon is observed in denervated hearts and isolated cardiac muscle, as well as in intact hearts; therefore, it represents an intrinsic change in inotropy. A sudden increase in aortic pressure, for example, causes a rapid increase in left ventricular end-diastolic volume. This leads to an initial increase in the contractile force of the ventricle through the Frank-Starling mechanism. If the increased afterload is maintained for 10–15 minutes, the force of contraction increases further, and in the intact heart, the end-diastolic volume decreases. This delayed increase in ventricular contractile force represents an increase in inotropy. The functional significance of the Anrep effect is that the increased inotropy partially compensates for the increased end-systolic volume and decreased stroke volume caused by the increase in afterload. Without this mechanism, increases in afterload would cause greater reductions in stroke volume than what is normally observed.
The mechanisms responsible for the initial response and the delayed response appear to be different. The initial increase in contractile force (Frank-Starling mechanism) is due to increased troponin C sensitivity to calcium. The delayed response likely involves several mechanisms that promote increased release of calcium by the sarcoplasmic reticulum. Suggested mediators include the release of endothelin-1 and angiotensin II by cardiac cells in response to stretch.