Abstract: AIM: To observe the effects of protein kinase-C (PKC) on the contractile function of hypertrophic hearts in transverse abdominal aortic constriction (TAC) rats in order to demonstrate whether PKC contributes as a pivotal node during the transition from cardiac hypertrophy to heart failure. METHODS: Twenty-four male Sprague Dawley rats were randomly divided into control and TAC groups. After 16 weeks, the hearts were rapidly removed and working-heart perfusion system and Millar probe were applied to monitor cardiac function. RESULTS: Hypertension, myocardial hypertrophy and an increase in cardiac output were observed in TAC rats. PMA, an agonist to PKC, reduced cardiac output and prolonged the time to peak pressure (TPP) and the time from peak to 75% relaxation (TR75), resulting in a depression in diastolic rate and inducing a sharp reduction in cardiac output at high heart rates. CONCLUSIONS: PMA activates PKC in hypertrophic hearts of 16-week TAC rats, which may lead to cardiac failure.