Abstract
Aim:
To quantitatively assess the effect of lowering external Ca2+ ([Ca2+]o) on both endothelium-dependent and -independent relaxations in rabbit aorta.
Methods:
Isometric contractions and relaxations of isolated aortae were recorded. When assessing the effect of reduced [Ca2+]o on relaxations, the normal [Ca2+]o solution was substituted with one of the reduced [Ca2+]o solutions for one aorta, while a paired aorta was replenished with normal [Ca2+]o solution.
Results:
The extent of acetylcholine (ACh)-induced relaxation, which is dependent on an intact endothelium, is time-dependent, and inversely related to [Ca2+]o in a range of 0.02–2 mmol/L. ACh-induced relaxations were not significantly altered by the magnitude of the precontraction induced by PGF2α. Nitroprusside-induced relaxations, which are independent of the endothelium, are also attenuated by reduced [Ca2+]o. Relaxant responses to ACh were significantly more susceptible to reduced [Ca2+]o than nitroprusside-induced relaxations. A maximally effective relaxing concentration of D600, an L-type Ca channel blocker methoxyverapamil, (10−5 mol/L) attenuated ACh-induced relaxations, whereas nitroprusside-induced relaxations were unaffected by D600.
Conclusion:
Thus, endothelium-dependent relaxation is more dependent on [Ca2+]o than endothelium-independent relaxation, and it seems likely that [Ca2+]o plays an important role not only in contractile processes, but also in relaxant processes as well.
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Acknowledgements
This work was supported by NHLBI grant NHL 26L2I. Methoxyverapamil (D600) was generously supplied by Knoll AG, Ludwigshafen, West Germany. The authors would like to thank Mrs Beth BECKER for her technical assistance and Mrs Patty SAMPSON for her kind assistance in preparation of the manuscript.
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Hayashi, S., Hester, R. Reduction in extracellular Ca2+ attenuates endothelium-dependent relaxation more than nitroprusside-induced relaxation. Acta Pharmacol Sin 31, 19–26 (2010). https://doi.org/10.1038/aps.2009.164
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DOI: https://doi.org/10.1038/aps.2009.164
