Inhibitory effect of sevoflurane pretreatment on angiotensin II -induced contraction of isolated rat aorta

Objective To determine the effects of sevoflurane (SEV) on angiotensin Ⅱ(AngⅡ)-induced contraction of isolated rat aorta with or without endothelium. Methods Sixty 4-10 week-old Wistar rats weighing 250-350 g were used. The animals were anesthetized with halothane and killed by exsanguination from carotid artery. The thoracic descending aortas were dissected. The adipose and connective tissue adherent to the aorta were carefully removed. The isolated aortas were cut into segments of 4 mm in length and mounted on isometric force transducer and bathed in Krebs bicarbonate solution (KBS) which was aerated with 95% O2/5% CO2. Aortic rings were stretched to a resting tension of 3.0 g. The viability of vascular smooth muscle cells was tested by contraction of aortic ring in response to KCl (3 × 10-2 mol · L-1) and the endothelial function was examined by phenylephedrine-induced vasoconstriction and acetylcholine-induced endothelium-dependent vasodilation. The aortic segments were divided into 2 groups: (1) endothelium-intact group ( + ET) and (2) endothelium-denuded group (- ET). The experiment was performed in 3 parts in both groups:(1) aortic segments were exposed to increasing concentrations of AngⅡ(10-9, 3 × 10-9, 10-8, 3 × 10-8, 10-7, 3 × 10-7, 10-6 mol·L-1) with or without 15 min SEV (5.1%) pretreatment to determine the effect of 5.1 % SEV pretreatment on Ang Ⅱ-induced contraction; (2) aortic rings were bathed in KBS containing 10-4 mol·L-1 L-NAME, a NOS inhibitor, for 15 min then exposed to Ang Ⅱ 10-7 mol·L-1 to determine if NO released from endothelium is involved in Ang Ⅱ-induced contraction; (3) aortic rings were first exposed to 1.7% , 3.4% or 5.1% SEV for 15 min then stimulated with Ang Ⅱ 10-7 mol·L-1 to determine if the inhibitory effect of SEV is dose-dependent.Results Ang Ⅱ elicited transient contraction in + ET aortic rings in a dose-dependent manner, reaching the maximal response at concentration of 10-7mol·L-1. Removal of endothelium significantly augmented Ang Ⅱ-induced contraction. The presence of L-NAME significantly enhanced Ang Ⅱ -yielded contraction in + ET rings comparable to the level of contraction in - ET rings, but did not potentiate the contraction in - ET rings. SEV inhibited Ang Ⅱ-induced contractile response of aortic + ET rings in a concentration-dependent manner. Removal of endothelium enhanced the inhibitory effect of SEV on Ang Ⅱ -induced contraction. Conclusion This study demonstrated that Ang Ⅱ elicites vascular smooth muscle contraction, but on the other hand, it also induces NO release from endothelium and vascular relaxation. Sevoflurane inhibits the dual actions of Ang Ⅱ in a dose-dependent manner.