The volatile anesthetic isoflurane attenuates Ca++ mobilization in cultured vascular smooth muscle cells.
Isoflurane is a volatile anesthetic which decreases vascular tone. Experiments were designed to determine whether isoflurane attenuated agonist-induced signaling in cultured vascular smooth muscle cells (A7r5). Cells were preincubated for 15 to 20 min with clinically relevant concentrations of isoflurane--0.5 to 2% in the gas phase and stimulated with 10(-9) or 10(-7) M vasopressin or with 3.3 x 10(-9) M platelet-derived growth factor. The two agonists are believed to act via differing signaling pathways. Total inositol phosphate formation was measured by column chromatography. Apparent intracellular free Ca++ concentration (1) [Ca++]i was estimated using indo-1 and flow cytometry. Isoflurane attenuated increases in [Ca++]i evoked by both agonists. Isoflurane 2.0% inhibited [Ca++]i responses evoked by vasopressin by 35 to 41%. Responses due to Ca++ release from intracellular stores were particularly sensitive to inhibition by isoflurane. The anesthetic attenuated inositol phosphate generation evoked by vasopressin and platelet-derived growth factor, suggesting a mechanism for isoflurane action on Ca++ release. Surprisingly, the anesthetic only modestly inhibited increases in [Ca++]i due to Ca++ entry. Isoflurane's effect on Ca++ influx after emptying of Ca++ stores was probed using thapsigargin. Inhibition of Ca++ influx was modest. It is suggested that isoflurane attenuates total inositol phosphate formation and Ca++ release evoked by vasopressin and platelet-derived growth factor while having limited effects on agonist-induced Ca++ entry.
Department of Anesthesia Research, Mayo Clinic, Rochester, Minnesota.
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Sill
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Eskuri
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Nelson
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Tarara
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Van Dyke
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D007530:Isoflurane / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014667:Vasopressins / Q000494:pharmacology
D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D013729:Terpenes; D014667:Vasopressins; D019284:Thapsigargin; D007530:Isoflurane; D002118:Calcium