title: Effects of cell-permeant calcium chelators on contractility in monkey basilar artery.
abstract: Vasospasm after traumatic or aneurysmal subarachnoid hemorrhage is associated with smooth muscle contraction, a process that results in part from increased intracellular calcium in smooth muscle cells. These experiments tested the hypothesis that chelation of intracellular calcium with the cell-permeant 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 calcium. Effects of BAPTA-AM on vasoconstriction induced by KCl, prostaglandin F2alpha (PGF2alpha), caffeine, and erythrocyte hemolysate were tested on monkey basilar artery under isometric tension. BAPTA-AM, 30 and 100 micromol/L, caused a significant decrease in resting tension in rings with and without endothelium (30 micromol/L; 8+/-6% [n.s.] and 14+/-5%, 100 micromol/L; 19+/-3% and 32+/-6%,p < 0.05, paired t test). Contractions to caffeine were significantly decreased by 30 micromol/L BAPTA-AM and were abolished at 100 micromol/L in rings with and without endothelium (p < 0.05). BAPTA-AM, 100 micromol/L, competitively inhibited contractions to PGF2alpha. BAPTA-AM, 100 micromol/L, significantly decreased the maximum contractions to KCI in rings with and without endothelium (p < 0.05). There were no significant effects of BAPTA-AM on contractions induced by hemolysate in rings with endothelium but in rings without endothelium, BAPTA-AM, 100 micromol/L, significantly inhibited contractions. In rings with endothelium contractions to hemolysate could be significantly reduced by BAPTA-AM plus indomethacin or indomethacin alone, suggesting that hemolysate releases an eicosanoid from the endothelium by a pathway that is not inhibited by BAPTA. These results suggest that the ability of BAPTA-AM to inhibit smooth muscle contractions will depend on the agonists mediating the contraction. In response to erythrocyte hemolysate, loading of endothelial cells with BAPTA-AM increases the release of a vasoconstricting eicosanoid from these cells that counteracts the decreased contraction caused by loading of smooth muscle cells with BAPTA-AM.
authors.affiliation: Section of Neurosurgery, University of Chicago Medical Center, Illinois 60637, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Macdonald
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: L S
authors.initials: LS
authors.lastname: Marton
authors.forename: B
authors.initials: B
authors.lastname: Weir
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004727:Endothelium / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008252:Macaca fascicularis; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010108:Oxyhemoglobins / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*