Propofol increases contractility during alpha1a-adrenoreceptor activation in adult rat cardiomyocytes.
BACKGROUND: The objective of this study was to identify the extent to which propofol alters intracellular free Ca2+ concentration ([Ca2+]i), myofilament Ca sensitivity, and contraction of individual cardiomyocytes during activation of alpha1a adrenoreceptors and to determine the cellular mechanism of action. METHODS: Freshly isolated ventricular myocytes were obtained from adult rat hearts. Myocyte shortening and [Ca2+]i were simultaneously monitored in individual cardiomyocytes exposed to phenylephrine after treatment with chloroethylclonidine (alpha1b-adrenoreceptor antagonist) and BMY 7378 (alpha1d-adrenoreceptor antagonist). Data are reported as mean +/- SD. RESULTS: Phenylephrine increased myocyte shortening by 124 +/- 9% (P = 0.002), whereas peak [Ca2+]i only increased by 8 +/- 3% (P = 0.110). Inhibition of phospholipase A2 and phospholipase C attenuated the phenylephrine-induced increase in shortening by 84 +/- 11% (P = 0.004) and 15 +/- 6% (P = 0.010), respectively. Inhibition of protein kinase C ( PKC) and Rho kinase attenuated the phenylephrine-induced increase in shortening by 17 +/- 8% (P = 0.010) and 74 +/- 13% (P = 0.006), respectively. In the presence of phenylephrine, propofol increased shortening by 40 +/- 6% (P = 0.002), with no concomitant increase in [Ca2+]i. PKC inhibition prevented the propofol-induced increase in shortening. Selective inhibition of PKCalpha, PKCdelta, PKCepsilon, and PKCzeta reduced the propofol-induced increase in shortening by 12 +/- 5% (P = 0.011), 36 +/- 8% (P = 0.001), 32 +/- 9% (P = 0.007), and 19 +/- 5% (P = 0.008), respectively. Na+ - H+ exchange inhibition reduced the propofol-induced increase in shortening by 56 +/- 7% (P = 0.001). CONCLUSION: Activation of alpha1a adrenoreceptors increases cardiomyocyte shortening primarily via a phospholipase A2-dependent, Rho kinase-dependent increase in myofilament Ca2+ sensitivity. Propofol further increases myofilament Ca2+ sensitivity and shortening via a PKC-dependent pathway and an increase in Na+ - H+ exchange activity.[1]References
- Propofol increases contractility during alpha1a-adrenoreceptor activation in adult rat cardiomyocytes. Gable, B.D., Shiga, T., Murray, P.A., Damron, D.S. Anesthesiology (2005) [Pubmed]
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