Influence of norepinephrine-sensitive intracellular calcium stores on the relaxant response to diltiazem in rat aorta.

The contractile response to norepinephrine (NE) in rat aorta has an initial fast (F) component attributable to Ca release, followed by a slow (S) component due to Ca influx. The relaxant action of the Ca entry blocker Diltiazem (DT) 10 microns was measured in three different responses to NE: a) a NE contraction in Ca = 1.35 mM (in which both the F and S components participate) was relaxed by 36 +/- 4%; b) previous incubation with Prazosin 0.01 microM eliminated the F component. Only the S component appeared (with a force equal to that of the previous total response) and it was relaxed by DT by 47 +/- 3%; c) the intracellular Ca pool was depleted by exposure to NE in Ca-free solution + EGTA. Further exposure to Ca = 1.35 mM produced only an S component, which was relaxed by DT by 61 +/- 4%. Since the preceding experiments suggested that the relaxant effect of DT increased as the participation of the Ca pool in the NE response decreased, an intermediate situation was looked for. The Ca pool was depleted as in (c) and then it was partially refilled by brief exposure to Ca = 1.35 mM. DT relaxation decreased to 51 +/- 3% (20 sec of refilling) and to 41 +/- 3% (60 sec of refilling). Similar results were obtained with DT 0.1, 1 and 100 microM. It is concluded that the relaxant action of DT on a NE contraction in rat aorta is inversely related to the amount of NE-releasable intracellular Ca that contributed to that contraction.