Reduction in extracellular Ca2+ attenuates endothelium- dependent relaxation more than nitroprussideinduced relaxation
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.
Keywords:
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.