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.
Wikman-Coffelt
J
J
Department of Medicine, University of California San Francisco 94143.
Wu
S T
ST
Parmley
W W
WW
Mason
D T
DT
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003864:Depression, Chemical; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D005470:Fluorometry; D006321:Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004075:Diglycerides; D000804:Angiotensin II; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium