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C 2 ‐ceramide attenuates phenylephrine‐induced vasoconstriction and elevation in [Ca 2+ ] i in rat aortic smooth muscle
Author(s) -
Zheng Tao,
Li Wenyan,
Wang Jun,
Altura Bella T.,
Altura Burton M.
Publication year - 1999
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-999-0414-4
Subject(s) - ceramide , lipidology , phenylephrine , vasoconstriction , chemistry , medicine , smooth muscle , clinical chemistry , cardiology , biochemistry , apoptosis , blood pressure
In the present study, we examined the effects of cell‐permeable C 2 ‐ceramide on contraction of aortic smooth muscle and intracellular free Ca 2+ ([Ca 2+ ] i ). C 2 ‐ceramide (10 −7 to 10 −4 M) alone did not elicit any significant changes in either basal tension or resting levels of [Ca 2+ ] i in rat aortic smooth muscle. However, C 2 ‐ceramide (10 −7 to 10 −4 M) attenuated phenylephrine‐induced contractions in isolated rat aortic rings in a concentration‐related manner, and inhibited elevations in [Ca 2+ ] i in cultured rat aortic smooth muscle cells induced by phenylephrine. C 2 ‐ceramide‐induced relaxation was found to be only slightly endothelium‐dependent. However, nitric oxide inhibitors ( l ‐NNA, l ‐NMMA), an inhibitor of prostanoid synthesis (indomethacin), an inhibitor of opiate actions, and several inhibitors of the pharmacologic actions of various vasoactive amines all failed to interfere with the vasorelaxant responses of C 2 ‐ceramide. Three different inhibitors of protein kinase C, when used in a wide concentration range, also failed to interfere with the ceramide‐induced relaxations. Our results suggest that the sphingomyelin‐signaling pathway may play an important regulatory role in arterial wall tone.