title: Sphingomyelinase and ceramide analogs induce contraction and rises in [Ca(2+)](i) in canine cerebral vascular muscle.
abstract: Studies were designed to investigate effects of neutral sphingomyelinase (N-SMase) and ceramide analogs as well as phosphorylcholine on vascular tone and Ca(2+) mobilization in isolated canine cerebral arterial smooth muscle. N-SMase (0.001-0.1 U/ml) provoked a gradual but sustained vasoconstriction of arterial rings in a concentration-related manner that was endothelium independent. Incubation of denuded arterial rings in Ca(2+)-free medium or pretreatment with verapamil in extracellular Ca(2+) resulted in a reduction of the N-SMase-evoked constriction. Exposure of arterial rings to 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid (BAPTA)-AM did not, however, result in a reduction of N-SMase-induced constriction. Both staurosporine and bisindolymaleimide I attenuated N-SMase-induced contractions to 66% and 72% of control, respectively. N-SMase caused gradual and sustained rises in intracellular Ca(2+) concentration ([Ca(2+)](i)) in primary cultured cerebral vascular smooth muscle cells. Pretreatment of these cultured cells with nimodipine and verapamil caused a steady decline in N-SMase-induced rises in [Ca(2+)](i). Exposure of the cells to Ca(2+)-free solution reversed the [Ca(2+)](i)-induced rise triggered by N-SMase to the resting baseline. Both C(8) and C(16) ceramide (10(-9)-10(-6) M), but not phosphorylcholine, constricted denuded canine arterial rings in a concentration-related manner and elevated [Ca(2+)](i). Our results suggest that the sphingomyelin-signaling pathway, via a probable release of ceramide molecules, may play an important role in regulation of cerebral arterial wall tone.
authors.affiliation: Department of Physiology, State University of New York, Health Science Center at Brooklyn, Brooklyn, New York 11203, USA.
authors.forename: T
authors.initials: T
authors.lastname: Zheng
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: B T
authors.initials: BT
authors.lastname: Altura
authors.forename: B M
authors.initials: BM
authors.lastname: Altura
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001488:Basilar Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism* / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology; D010767:Phosphorylcholine / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D001381:Azepines; D002121:Calcium Channel Blockers; D002518:Ceramides; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; C056218:ML 9; D010767:Phosphorylcholine; D009553:Nimodipine; D011493:Protein Kinase C; D013108:Sphingomyelin Phosphodiesterase; D002118:Calcium