Effects of cell-permeant calcium chelators on contractility in monkey basilar artery

Vasospasm after traumatic or aneurysmal subarachnoid hemorrhage is associat ed with smooth muscle contraction, a process that results in part from incr eased intracellular calcium in smooth muscle cells. These experiments teste d the hypothesis that chelation of intracellular calcium with the cell-perm eant calcium chelator, 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetracetic acid acetoxymethyl ester (BAPTA-AM), decreases smooth muscle contraction in response to agents that cause contraction by increasing intracellular calc ium. Effects of BAPTA-AM on vasoconstriction induced by KCl, prostaglandin F-2 alpha (PGF(2 alpha)), caffeine, and erythrocyte hemolysate were tested on monkey basilar artery under isometric tension. BAPTA-AM, 30 and 100 mu m ol/L, caused a significant decrease in resting tension in rings with and wi thout endothelium (30 mu mol/L; 8 +/- 6% [n.s.] and 14 +/- 5%, 100 mu mol/L ; 19 +/- 3% and 32 +/- 6%, p < 0.05, paired t test). Contractions to caffei ne were significantly decreased by 30 mu mol/L BAPTA-AM and were abolished at 100 mu mol/L in rings with and without endothelium (p < 0.05). BAPTA-AM, 100 mu mol/L, competitively inhibited contractions to PGF(2 alpha). BAPTA- AM, 100 mu mol/L, significantly decreased the maximum contractions to KCl i n rings with and without endothelium (p < 0.05). There were no significant effects of BAPTA-AM on contractions induced by hemolysate in rings with end othelium but in rings without endothelium, BAPTA-AM, 100 mu mol/L, signific antly inhibited contractions. In rings with endothelium contractions to hem olysate could be significantly reduced by BAPTA-AM plus indomethacin or ind omethacin alone, suggesting that hemolysate releases an eicosanoid from the endothelium by a pathway that is not inhibited by BAPTA. These results sug gest that the ability of BAPTA-AM to inhibit smooth muscle contractions wil l depend on the agonists mediating the contraction. In response to erythroc yte hemolysate, loading of endothelial cells with BAPTA-AM increases the re lease of a vasoconstricting eicosanoid from these cells that counteracts th e decreased contraction caused by loading of smooth muscle cells with BAPTA -AM.