Reduction in extracellular Ca^2＋ attenuates endothelium-dependent relaxation more than nitroprussideinduced relaxation

Reduction in extracellular Ca2+ attenuates endothelium-dependent relaxation more than nitroprusside-induced relaxation

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 PGF_2α. 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.