CA2-DEPENDENCE OF VASOCONSTRICTION MEDIATED BY ALPHA(1A)-ADRENOCEPTORS IN PERFUSED RAT HINDLIMB - A PHARMACOLOGICAL APPROACH()

We investigated the source of Ca2+ for the vasoconstriction mediated b y alpha(1a)-adrenoceptors in perfused rat hindlimb in functional studi es. The noradrenaline (NA)-induced maximum response was decreased by 9 2% following perfusion with Ca2+-free medium. Depletion of intracellul ar Ca2+-stores with repeatedly application of caffeine and NA in Ca2+- free medium resulted in complete abolishment of NA-response. Nifedipin e concentration-dependently inhibited NA-contraction with a maximum in hibition of 65%. The residual nifedipine-insensitive response was furt her inhibited by Cd2+. Following depletion of Ca2+ stores with cyclopi azonic acid in Ca2+ free medium for 30 min, the NA-response obtained b y re-admission of Ca2+ was decreased by 80%. However, re-introduction of Ca2+ to NA-treated tissues in Ca2+-free medium without prior treatm ent with cyclopiazonic acid normalizes the NA-response. These results suggest that the NA-contraction in this preparation is mediated largel y via an influx of-extracellular Ca2+, of which the majority utilizes L-type calcium channels. Only a small portion of the contractile respo nse to NA is derived from intracellular stores, which probably also pl ay a modulatory role on Ca2+ influx. (C) 1998 Elsevier Science Inc.