Angiotensin II (ANG II) plays a major role in the development of cardiac hypertrophy through its AT1 receptor subtype; whereas angiotensin-converting enzyme (ACE) inhibitors are effective in reversing ANG II's effects on the heart. The objective is to investigate the role of PKA and PKC in the contractile response of atrial tissue during development and ACE inhibitor-induced regression of eccentric hypertrophy; induced by the aortocaval shunt method. One week post-surgery, sham and shunt rats were divided into captopril-treated and untreated group for 2 weeks. Afterwhich, isometric contraction was assessed by electrical stimulation of isolated rat left atrial preparations superfused with Tyrode solution in the presence or absence of specific inhibitor, KT 5720 for PKA, Ro-320432 for PKC, and high calcium. Peak tension developed (PTD) was greater in shunt hearts compared to sham ones. However, when expressed to relative tissue mass, hypertrophied muscle showed weaker contraction than the sham. In sham rats, PTD was more affected by PKC- than PKA-inhibition; whereas this differential effect was reduced in the hypertrophied heart. Treatment of shunt rats with captopril regressed left atrial hypertrophy by 67% and restored PKC/PKA differential responsiveness towards sham levels. In the hypertrophied left atria, there is an increase in the velocity of contraction and relaxation that was not evident when expressed in specific relative terms. Treatment with ACE inhibitor increased the specific velocity of contraction in the shunt along with its higher PKC sensitivity. We conclude that ACE inhibition during eccentric cardiac hypertrophy produces a negative trophic and a positive inotropic effect mainly through a PKC-dependent mechanism.