Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Aug 2006
Comparative StudyReduced sinoatrial cAMP content plays a role in postnatal heart rate slowing in the rabbit.
1. Decreasing heart rate during development is known to be the result of parasympathetic nervous system maturation that depresses the pacemaker current (If) by acetylcholine (ACh). However, a direct effect of ACh on If has been ruled out and the involvement of other secondary messengers, such as cAMP, was verified in previous studies. ⋯ Significantly reduced heart rate, but unchanged HRV, was observed in perfused hearts in the older age groups, accompanied with a slowed phase 4 spontaneous depolarization rate (90.5 +/- 4.7 vs 49.6 +/- 2.6 mV/s for 2 week vs 4 week hearts, respectively; n = 5; P < 0.05), a negative shift of the If threshold potential (-45.5 +/- 3.0 vs -51.1 +/- 6.0 mV for 2 week vs 4 week hearts, respectively; n = 9; P < 0.05) and decreasing basal levels of SA nodal cAMP (0.31 +/- 0.05 vs 0.025 +/- 0.002 micromol/L for 2 week vs 4 week hearts, respectively; n = 6; P < 0.05). Gene expression levels of PDE1A, 4A and 8A were increased in the 12 week group compared with the 2 week group 1.5-, 2- and 1.8-fold, respectively (P < 0.05), with little change in ADCY1 and 5. 4. These data suggest that, in addition to autonomic innervation, slowing of heart rate during postnatal maturation can be attributed to a negative shift of the If activation caused by diminished baseline cAMP content in SA nodal cells.
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Clin. Exp. Pharmacol. Physiol. · Aug 2006
Comparative StudyCarnitine esters prevent oxidative stress damage and energy depletion following transient forebrain ischaemia in the rat hippocampus.
1. The present study investigated whether propionyl-L-carnitine (PLC) has neuroprotective effects, similar to those reported for acetyl-L-carnitine (AC), against transient forebrain ischaemia-induced neuronal damage and biochemical derangement in the rat hippocampal CA1 region. 2. In total, 105 adult male Wistar albino rats were divided into seven groups of 15 animals each. ⋯ Results from the present study suggest, for the first time, that PLC attenuates forebrain ischaemia-induced neuronal injury, oxidative stress and energy depletion in the hippocampal CA1 region. Propionyl-L-carnitine has neuroprotective effects similar to AC and could have a potential use in the treatment of neurodegenerative diseases. 7. The results of the present study will open up new perspectives for the use of PLC in the treatment of neurodegenerative diseases associated with, or secondary to, myocardial ischaemia-reperfusion injury and chronic circulatory failure.