EFFECTS OF DIFFERENT AGENTS ON THE CONTRACTILE RESPONSE ELICITED BY EXTRACELLULAR CALCIUM AFTER DEPLETION OF INTERNAL CALCIUM STORES IN RATISOLATED AORTA

Noradrenaline, 1 muM, induced a sustained contractile response in rat isolated aorta in the presence and in the absence of extracellular Ca2 +. After depleting the noradrenaline-sensitive intracellular Ca2+ stor es, an increase in the basal tone of the aorta was observed during the incubation period in the presence of Ca2+ and in the absence of the a gonist. We have tested the possible pathways through which Ca2+ enters the cell to refill the previously depleted Ca2+ pools, a process that is accompanied by an increase in tension. The magnitude of this incre ase does not depend on the presence of Mg2+ in the extracellular mediu m nor on the temperature, suggesting that it is mediated by an event t hat does not depend on intracellular energy or Ca2+, Mg2+-ATPase. It i s inhibited in a concentration-dependent manner by an unspecific relax ing compound, caffeine, and an organic Ca2+ entry blocker, verapamil, but not by an inorganic Ca2+ entry blocker, lanthanum. Caffeine (10 mm ) and verapamil (10(-5) M) completely inhibited the increase in the re sting tone, but only verapamil abolished the refilling of the noradren aline-sensitive Ca2+ pools, indicating that the extracellular Ca2+ ent ers the cell through voltage-operated Ca2+ channels. Caffeine inhibite d the increase in the resting tone without blocking the refilling proc ess of the stores at 37-degrees-C, but at 25-degrees-C a partial inhib ition of the repletion of internal Ca2+ pools was observed. These resu lts confirm previous work that showed a temperature-dependent activity of caffeine.