Isoflurane alters angiotensin II-induced Ca 2+ mobilization in aortic smooth muscle cells from hypertensive rats: Implication of cytoskeleton

Abstract

Background: Angiotensin II (AngII) is a potent vasoconstrictor involved in the short-term control of arterial blood pressure. Isoflurane was reported to decrease vascular tone through an alteration of vascular smooth muscle cell vasomotor response to several agonists, but its effect on AngII signaling is not known. On the other hand, vascular response to AngII is altered in hypertension. In this study, the authors tested the hypothesis that (1) isoflurane alters AngII-induced intracellular Ca 2+ mobilization in aortic vascular smooth muscle cell from Wistar Kyoto and spontaneously hypertensive rats, and (2) this effect could be associated with an alteration of the organization of microtubular network, reported to be involved in AngII signaling. Methods: The effect of 0.5-3% isoflurane was studied (1) on AngII (10 -6 M)-induced intracellular Ca 2+ mobilization, intracellular Ca 2+ release from internal stores, and Ca 2+ influx in Fura-2 loaded cultured aortic vascular smooth muscle cell isolated from 6-week-old Wistar Kyoto and spontaneously hypertensive rats, using fluorescent imaging microscopy; and (2) on the organization of cytoskeletal elements, using immunofluorescence labeling. Results: In both stains, isoflurane decreased in a concentration-dependent manner AngII-induced intracellular Ca 2+ mobilization, Ca 2+ release from internal stores, and C 2+ influx through nifedipine-insensitive Ca 2+ channels. This effect occurred at a lower concentrations of isoflurane in Wistar Kyoto rats than in spontaneously hypertensive rats. In both strains, the effect of isoflurane on AngII-Ca 2+ mobilization was abolished by impairment with nocodazole, vinblastine, or paclitaxel of microtubules polymerization. Isoflurane directly altered tubular network organization in a concentration-dependent and reversible manner. Conclusions: Isoflurane decreased AngH-induced Ca 2+ mobilization at clinically relevant concentrations, suggesting that vascular response to AngH could be altered during isoflurane anesthesia. The hypertensive strain was found less sensitive than the normotensive one. In both strains, the isoflurane effect was associated with a microtubular network interaction.