Angiotensin II and phorbol esters depress cardiac performance and decrease diastolic and systolic [Ca2+]i in isolated perfused rat hearts.

Both angiotensin II and the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), significantly depressed developed pressure, oxygen consumption, and coronary flow in isolated perfused rat hearts and caused a decrease in diastolic and systolic [Ca2+]i and [Ca2+]i transients. PMA and angiotensin II did not change the levels of cAMP but moderately decreased PCr/Cr. The decrease in systolic [Ca2+]i and amplitude of [Ca2+]i transients caused by PMA and angiotensin II resulted in depressed cardiac function. Hearts perfused with PMA and angiotensin II had a decreased sensitivity to extracellular calcium. Depressed developed pressure and oxygen consumption in the PMA- and angiotensin II-treated hearts may have been due to a decrease in amplitude of effective [Ca2+]i transients, because the [Ca2+]i threshold for cross-bridge interaction was presumably higher than the diastolic [Ca2+]i in these hearts.