Effects of LP-805, a new vasodilating agent, on cytosolic Ca2+ and contraction in vascular smooth muscle of rat aorta

Abstract

1. LP-805 (0.1-10 microM) 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 Ca(2+)-free solution, LP-805 (0.1-10 microM) markedly inhibited the phasic contraction induced by 0.3 microM NE and the contraction induced by Ca2+ (0.1-2 mM) in the presence of 0.3 microM NE, in a concentration-dependent manner. Similar results were obtained in the presence of 5-HT (10 microM) or PGF2 alpha (10 microM). 3. In fura-2 loaded strips, ryanodine (10 microM) and LP-805 (10 microM) abolished 1 microM NE- and 30 microM 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.