The cyclooxygenase-2 product prostaglandin E2 modulates cardiac contractile function in adult rat ventricular cardiomyocytes.
Prostaglandin E(2) (PGE(2)), a product of the cyclooxygenase-2 pathway, has been shown to increase cardiac output and modulate cardiac contractile function. However, whether the cardiac contractile response of PGE(2) is due to its action on single ventricular myocytes has not been elucidated. To assess the mechanical effect of PGE(2) at the cellular level, adult rat ventricular myocytes were isolated and stimulated to contract at 0.5Hz. Mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix Myocam analog-to-digital optical detection system. Contractile and intracellular Ca(2+) properties were evaluated as peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), maximal velocity of shortening or relengthening (+/-dL/dt) and Ca(2+)-induced intracellular Ca(2+) fluorescence release (CICR), baseline intracellular Ca(2+) levels and intracellular Ca(2+) decay rate (tau). PGE(2) (10(-8) to 10(-3)M) elicited an augmentation in PS but had no effect on TPS, TR(90), +/-dL/dt, CICR and tau. High concentration of PGE(2) (10(-5)M or higher) reduced the baseline intracellular Ca(2+) levels. These data indicate that the myocardial contractile response of PGE(2) may be due to its direct cardiac contractile action at the single ventricular myocyte level, probably through a mechanism independent of intracellular Ca(2+) release.
Klein
Aaron L
AL
Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA.
Wold
Loren E
LE
Ren
Jun
J
D000818:Animals; D002118:Calcium / Q000032:analysis; D002413:Cations, Divalent; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000494:pharmacology* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006352:Heart Ventricles; D006706:Homeostasis; D007527:Isoenzymes / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D051381:Rats
D002413:Cations, Divalent; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D002118:Calcium