EFFECTS OF LP-805, A NEW VASODILATING AGENT, ON CYTOSOLIC CA2+ AND CONTRACTION IN VASCULAR SMOOTH-MUSCLE OF RAT AORTA

1. LP-805 (0.1-10-mu-M) caused the reduction in norepinephrine (NE)-and serotonin (5-HT)-induced maximum response, a parallel shift of the concentration-response curve for prostaglandin-F2-alpha (PGF2-alpha), in a concentration-dependent manner, but not K+-induced maximum response. 2. In Ca2+-free solution, LP-805 (0.1-1)mu-M) markedly inhibited the phasic contraction induced by 0.3-mu-M NE and the contraction induced by Ca2+ (0.1-2 mM) in the presence of 0.3-mu-M NE, in a concentration-dependent manner. Similar results were obtained in the presence of 5-HT(10-mu-M)or PGF2 alpha (10-mu-M). 3. In fura-2 loaded strips, ryanodine (10-mu-M) and LP-805 (10-mu-M) abolished 1-mu-M NE- and 30-mu-M 5-HT-induced phasic contractions, and inhibited the increase in cytosolic Ca2+ levels by both the agonists in the absence of external Ca2+, but had no influence on the following sustained contractions. 4. The effects of LP-805 on PGF2 alpha-induced Ca2+ transient and large sustained contraction were similar to those of ryanodine. 5. These results suggest that a vasodilatory effect of LP-805 might account for inhibiting the mobilization of external Ca2+ through receptor mediated passway and the Ca2+ release from a ryanodine sensitive Ca2+ store.