Key result
Combined inhibition of PDE3 and PDE4, but not individual inhibition, attenuated ET1-induced PKD activation and increased PLB and cTnI phosphorylation in adult rat ventricular myocytes.
Population
Adult rat ventricular myocytes (ARVM) isolated from adult male Wistar rats (250 g)
Comparison
Selective and non-selective phosphodiesterase… vs Vehicle control
Design
Preclinical
Authors
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Hypothesis-generating in rat myocytes; clinical relevance of dual PDE3/PDE4 inhibition requires human validation.
p-value: p=<0.05
In adult rat ventricular myocytes, cAMP pools controlled by PDE3 and PDE4 play redundant roles in regulating PKA activity that inhibits ET1-induced PKD activation.
Haworth et al. (2010) studied Myocardial PKD activation (preclinical). Combined PDE3 and PDE4 inhibition (cilostamide and rolipram) vs. Vehicle or individual PDE inhibitors was evaluated on ET1-induced PKD activation (phosphorylation at Ser916 and Ser744/748) (p=<0.05). Combined inhibition of PDE3 and PDE4, but not individual inhibition, attenuated ET1-induced PKD activation and increased PLB and cTnI phosphorylation in adult rat ventricular myocytes.
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