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

To quantitatively assess the effect of lowering external Ca(2+) ([Ca(2+)](o)) on both endothelium-dependent and -independent relaxations in rabbit aorta. Isometric contractions and relaxations of isolated aortae were recorded. When assessing the effect of reduced [Ca(2+)](o) on relaxations, the normal [Ca(2+)](o) solution was substituted with one of the reduced [Ca(2+)](o) solutions for one aorta, while a paired aorta was replenished with normal [Ca(2+)](o) solution. The extent of acetylcholine (ACh)-induced relaxation, which is dependent on an intact endothelium, is time-dependent, and inversely related to [Ca(2+)](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(2alpha). Nitroprusside-induced relaxations, which are independent of the endothelium, are also attenuated by reduced [Ca(2+)](o). Relaxant responses to ACh were significantly more susceptible to reduced [Ca(2+)](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. Thus, endothelium-dependent relaxation is more dependent on [Ca(2+)](o) than endothelium-independent relaxation, and it seems likely that [Ca(2+)](o) plays an important role not only in contractile processes, but also in relaxant processes as well.