abstract
- We investigated the source of Ca2+ for the vasoconstriction mediated by alpha1a-adrenoceptors in perfused rat hindlimb in functional studies. The noradrenaline (NA)-induced maximum response was decreased by 92% following perfusion with Ca2+-free medium. Depletion of intracellular Ca2+-stores with repeatedly application of caffeine and NA in Ca2+-free medium resulted in complete abolishment of NA-response. Nifedipine concentration-dependently inhibited NA-contraction with a maximum inhibition of 65%. The residual nifedipine-insensitive response was further inhibited by Cd2+. Following depletion of Ca2+ stores with cyclopiazonic acid in Ca2+ free medium for 30 min, the NA-response obtained by re-admission of Ca2+ was decreased by 80%. However, re-introduction of Ca2+ to NA-treated tissues in Ca2+-free medium without prior treatment with cyclopiazonic acid normalizes the NA-response. These results suggest that the NA-contraction in this preparation is mediated largely via an influx of extracellular Ca2+, of which the majority utilizes L-type calcium channels. Only a small portion of the contractile response to NA is derived from intracellular stores, which probably also play a modulatory role on Ca2+ influx.